Drug Information

Drug (ID: DG00011) and It's Reported Resistant Information
Name
Dolutegravir
Synonyms
1051375-16-6; GSK1349572; Tivicay; S/GSK1349572; Dolutegravir (GSK1349572); S-349572; GSK-1349572; GSK 1349572; UNII-DKO1W9H7M1; (4r,12as)-N-(2,4-Difluorobenzyl)-7-Hydroxy-4-Methyl-6,8-Dioxo-3,4,6,8,12,12a-Hexahydro-2h-Pyrido[1',2':4,5]pyrazino[2,1-B][1,3]oxazine-9-Carboxamide; CHEBI:76010; DKO1W9H7M1; Tivicay (TN); (4R,12aS)-N-[(2,4-Difluorophenyl)methyl]-3,4,6,8,12,12a-hexahydro-7-hydroxy-4-methyl-6,8-dioxo-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide; Dolutegravir Sodium (
    Click to Show/Hide
Indication
In total 1 Indication(s)
Human immunodeficiency virus disease [ICD-11: 1C60-1C62]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
HIV infection [ICD-11: 1C62]
[2]
Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
HIV infection [ICD-11: 1C62]
[3]
Target Human immunodeficiency virus Integrase (HIV IN) POL_HV1B1 [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C20H19F2N3O5
IsoSMILES
C[C@@H]1CCO[C@@H]2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)O
InChI
1S/C20H19F2N3O5/c1-10-4-5-30-15-9-24-8-13(17(26)18(27)16(24)20(29)25(10)15)19(28)23-7-11-2-3-12(21)6-14(11)22/h2-3,6,8,10,15,27H,4-5,7,9H2,1H3,(H,23,28)/t10-,15+/m1/s1
InChIKey
RHWKPHLQXYSBKR-BMIGLBTASA-N
PubChem CID
54726191
ChEBI ID
CHEBI:76010
TTD Drug ID
D00YZD
VARIDT ID
DR00383
DrugBank ID
DB08930
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-01: Infectious/parasitic diseases
Click to Show/Hide the Resistance Disease of This Class
HIV infection [ICD-11: 1C62]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.S123G+p.T124A+p.K127R+p.G140S+p.Q148K+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.585
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.85
TM score: 0.94865
Amino acid change:
E10D+I72V+S123G+T124A+K127R+G140S+Q148K+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
10
|
E
D
E
E
H
H
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
20
|
R
R
A
A
M
M
A
A
S
S
D
D
F
F
N
N
L
L
P
P
30
|
P
P
V
V
V
V
A
A
K
K
E
E
I
I
V
V
A
A
S
S
40
|
C
C
D
D
K
K
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
50
|
M
M
H
H
G
G
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
60
|
I
I
W
W
Q
Q
L
L
D
D
C
C
T
T
H
H
L
L
E
E
70
|
G
G
K
K
I
V
I
I
L
L
V
V
A
A
V
V
H
H
V
V
80
|
A
A
S
S
G
G
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
90
|
P
P
A
A
E
E
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
100
|
F
F
L
L
L
L
K
K
L
L
A
A
G
G
R
R
W
W
P
P
110
|
V
V
K
K
T
T
I
I
H
H
T
T
D
D
N
N
G
G
S
S
120
|
N
N
F
F
T
T
S
G
T
A
T
T
V
V
K
R
A
A
A
A
130
|
C
C
W
W
W
W
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
140
|
G
S
I
I
P
P
Y
Y
N
N
P
P
Q
Q
S
S
Q
K
G
G
150
|
V
V
V
V
E
E
S
S
M
M
N
N
K
K
E
E
L
L
K
K
160
|
K
K
I
I
I
I
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
170
|
E
E
H
H
L
L
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
180
|
V
V
F
F
I
I
H
H
N
N
F
F
K
K
R
R
K
K
G
G
190
|
G
G
I
I
G
G
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
200
|
I
I
V
V
D
D
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
210
|
T
T
K
K
E
E
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
220
|
I
I
Q
Q
N
N
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
230
|
S
S
R
R
D
N
P
P
L
L
W
W
K
K
G
G
P
P
A
A
240
|
K
K
L
L
L
L
W
W
K
K
G
G
E
E
G
G
A
A
V
V
250
|
V
V
I
I
Q
Q
D
D
N
N
S
S
D
D
I
I
K
K
V
V
260
|
V
V
P
P
R
R
R
R
K
K
A
A
K
K
I
I
I
I
R
R
270
|
D
D
Y
Y
G
G
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
280
|
C
C
V
V
A
A
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E296Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.S17T+p.S39N+p.I72V+p.S119P+p.T122I+p.T124N+p.T125A+p.V151I+p.N155H+p.N222K+p.P261A
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.551
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.9
TM score: 0.94823
Amino acid change:
E10D+S17T+S39N+I72V+S119P+T122I+T124N+T125A+V151I+N155H+N222K+P261A
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
10
|
E
D
E
E
H
H
E
E
K
K
Y
Y
H
H
S
T
N
N
W
W
20
|
R
R
A
A
M
M
A
A
S
S
D
D
F
F
N
N
L
L
P
P
30
|
P
P
V
V
V
V
A
A
K
K
E
E
I
I
V
V
A
A
S
N
40
|
C
C
D
D
K
K
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
50
|
M
M
H
H
G
G
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
60
|
I
I
W
W
Q
Q
L
L
D
D
C
C
T
T
H
H
L
L
E
E
70
|
G
G
K
K
I
V
I
I
L
L
V
V
A
A
V
V
H
H
V
V
80
|
A
A
S
S
G
G
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
90
|
P
P
A
A
E
E
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
100
|
F
F
L
L
L
L
K
K
L
L
A
A
G
G
R
R
W
W
P
P
110
|
V
V
K
K
T
T
I
I
H
H
T
T
D
D
N
N
G
G
S
P
120
|
N
N
F
F
T
I
G
G
T
N
T
A
V
V
R
R
A
A
A
A
130
|
C
C
W
W
W
W
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
140
|
G
G
I
I
P
P
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
150
|
V
V
V
I
E
E
S
S
M
M
N
H
K
K
E
E
L
L
K
K
160
|
K
K
I
I
I
I
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
170
|
E
E
H
H
L
L
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
180
|
V
V
F
F
I
I
H
H
N
N
F
F
K
K
R
R
K
K
G
G
190
|
G
G
I
I
G
G
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
200
|
I
I
V
V
D
D
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
210
|
T
T
K
K
E
E
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
220
|
I
I
Q
Q
N
K
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
230
|
S
S
R
R
N
N
P
P
L
L
W
W
K
K
G
G
P
P
A
A
240
|
K
K
L
L
L
L
W
W
K
K
G
G
E
E
G
G
A
A
V
V
250
|
V
V
I
I
Q
Q
D
D
N
N
S
S
D
D
I
I
K
K
V
V
260
|
V
V
P
A
R
R
R
R
K
K
A
A
K
K
I
I
I
I
R
R
270
|
D
D
Y
Y
G
G
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
280
|
C
C
V
V
A
A
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q194H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.D6T+p.K7E+p.S17N+p.V54I+p.I72V+p.L74M+p.V79I+p.T97A+p.L101I+p.I113L+p.S119R+p.T122I+p.T124N+p.T125A+p.E138K+p.G140A+p.I141AT+p.S147SG+p.Q148R+p.K156N+p.I203M+p.I208M+p.L234V+p.D253E
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.975
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.96
TM score: 0.94366
Amino acid change:
D6T+K7E+S17N+V54I+I72V+L74M+V79I+T97A+L101I+I113L+S119R+T122I+T124N+T125A+E138K+G140A+I141AT+S147G+Q148R+K156N+I203M+I208M+L234V+D253E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
D
D
G
G
I
I
D
T
K
E
A
A
Q
Q
10
|
D
D
E
E
H
H
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
20
|
R
R
A
A
M
M
A
A
S
S
D
D
F
F
N
N
L
L
P
P
30
|
P
P
V
V
V
V
A
A
K
K
E
E
I
I
V
V
A
A
S
S
40
|
C
C
D
D
K
K
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
50
|
M
M
H
H
G
G
Q
Q
V
I
D
D
C
C
S
S
P
P
G
G
60
|
I
I
W
W
Q
Q
L
L
D
D
C
C
T
T
H
H
L
L
E
E
70
|
G
G
K
K
I
V
I
I
L
M
V
V
A
A
V
V
H
H
V
I
80
|
A
A
S
S
G
G
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
90
|
P
P
A
A
E
E
T
T
G
G
Q
Q
E
E
T
A
A
A
Y
Y
100
|
F
F
L
I
L
L
K
K
L
L
A
A
G
G
R
R
W
W
P
P
110
|
V
V
K
K
T
T
I
L
H
H
T
T
D
D
N
N
G
G
S
R
120
|
N
N
F
F
T
I
G
G
T
N
T
A
V
V
R
R
A
A
A
A
130
|
C
C
W
W
W
W
A
A
G
G
I
I
K
K
Q
Q
E
K
F
F
140
|
G
A
I
A
P
P
Y
Y
N
N
P
P
Q
Q
S
G
Q
R
G
G
150
|
V
V
V
V
E
E
S
S
M
M
N
N
K
N
E
E
L
L
K
K
160
|
K
K
I
I
I
I
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
170
|
E
E
H
H
L
L
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
180
|
V
V
F
F
I
I
H
H
N
N
F
F
K
K
R
R
K
K
G
G
190
|
G
G
I
I
G
G
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
200
|
I
I
V
V
D
D
I
M
I
I
A
A
T
T
D
D
I
M
Q
Q
210
|
T
T
K
K
E
E
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
220
|
I
I
Q
Q
N
N
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
230
|
S
S
R
R
N
N
P
P
L
V
W
W
K
K
G
G
P
P
A
A
240
|
K
K
L
L
L
L
W
W
K
K
G
G
E
E
G
G
A
A
V
V
250
|
V
V
I
I
Q
Q
D
E
N
N
S
S
D
D
I
I
K
K
V
V
260
|
V
V
P
P
R
R
R
R
K
K
A
A
K
K
I
I
I
I
R
R
270
|
D
D
Y
Y
G
G
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
280
|
C
C
V
V
A
A
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q203H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.M154L+p.N155H+p.V201I+p.D232N+p.L242LF
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.66
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.98
TM score: 0.94753
Amino acid change:
S17N+M154L+N155H+V201I+D232N+L242F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
10
|
D
D
E
E
H
H
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
20
|
R
R
A
A
M
M
A
A
S
S
D
D
F
F
N
N
L
L
P
P
30
|
P
P
V
V
V
V
A
A
K
K
E
E
I
I
V
V
A
A
S
S
40
|
C
C
D
D
K
K
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
50
|
M
M
H
H
G
G
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
60
|
I
I
W
W
Q
Q
L
L
D
D
C
C
T
T
H
H
L
L
E
E
70
|
G
G
K
K
V
V
I
I
L
L
V
V
A
A
V
V
H
H
V
V
80
|
A
A
S
S
G
G
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
90
|
P
P
A
A
E
E
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
100
|
F
F
L
L
L
L
K
K
L
L
A
A
G
G
R
R
W
W
P
P
110
|
V
V
K
K
T
T
I
I
H
H
T
T
D
D
N
N
G
G
S
S
120
|
N
N
F
F
T
T
G
G
A
A
T
T
V
V
R
R
A
A
A
A
130
|
C
C
W
W
W
W
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
140
|
G
G
I
I
P
P
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
150
|
V
V
V
V
E
E
S
S
M
L
N
H
K
K
E
E
L
L
K
K
160
|
K
K
I
I
I
I
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
170
|
E
E
H
H
L
L
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
180
|
V
V
F
F
I
I
H
H
N
N
F
F
K
K
R
R
K
K
G
G
190
|
G
G
I
I
G
G
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
200
|
I
I
V
I
D
D
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
210
|
T
T
K
K
E
E
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
220
|
I
I
Q
Q
N
N
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
230
|
S
S
R
R
D
N
P
P
L
L
W
W
K
K
G
G
P
P
A
A
240
|
K
K
L
L
L
F
W
W
K
K
G
G
E
E
G
G
A
A
V
V
250
|
V
V
I
I
Q
Q
D
D
N
N
S
S
D
D
I
I
K
K
V
V
260
|
V
V
P
P
R
R
R
R
K
K
A
A
K
K
I
I
I
I
R
R
270
|
D
D
Y
Y
G
G
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
280
|
C
C
V
V
A
A
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q193H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.K14R+p.V31I+p.V32I+p.L45Q+p.L101I+p.T112V+p.T125A+p.G134N+p.I135V+p.K136T+p.Y143C+p.V201I+p.T206S+p.S230R+p.L234I+p.N254NS+p.R269K+p.D270H
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.008
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.12
TM score: 0.93557
Amino acid change:
K14R+V31I+V32I+L45Q+L101I+T112V+T125A+G134N+I135V+K136T+Y143C+V201I+T206S+S230R+L234I+N254S+R269K+D270H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
R
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
I
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
Q
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
V
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
N
I
V
K
T
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
C
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
S
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
R
R
R
N
N
1380
|
P
P
L
I
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
S
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
K
D
H
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q195H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E11D+p.K14R+p.S17T+p.V31I+p.L45V+p.A91S+p.L101I+p.T124A+p.E138Q+p.G140C+p.Q148R+p.V151I+p.K219N+p.N222K+p.L234I+p.V259I
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.772
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.15
TM score: 0.93594
Amino acid change:
E11D+K14R+S17T+V31I+L45V+A91S+L101I+T124A+E138Q+G140C+Q148R+V151I+K219N+N222K+L234I+V259I
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
D
H
H
1160
|
E
E
K
R
Y
Y
H
H
S
T
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
V
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
S
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
Q
F
F
G
C
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
R
G
G
V
V
V
I
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
N
I
I
Q
Q
N
K
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
I
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
I
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q201H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E11D+p.V31I+p.G70R+p.I84V+p.L101I+p.S119P+p.T122I+p.N155H+p.G163E+p.V201I+p.D256E
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.457
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.14
TM score: 0.94195
Amino acid change:
E11D+V31I+G70R+I84V+L101I+S119P+T122I+N155H+G163E+V201I+D256E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
D
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
R
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
V
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
P
N
N
F
F
T
I
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
H
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
E
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
E
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q198H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.K14R+p.S24G+p.D25E+p.S39C+p.I60IM+p.L63I+p.T97A+p.L101I+p.S119SR+p.T124N+p.T125A+p.I135V+p.E138T+p.G140S+p.Q148H+p.M154I+p.V165I+p.V201I+p.V259VI
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.011
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.86
TM score: 0.95222
Amino acid change:
K14R+S24G+D25E+S39C+I60M+L63I+T97A+L101I+S119R+T124N+T125A+I135V+E138T+G140S+Q148H+M154I+V165I+V201I+V259I
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
R
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
G
D
E
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
C
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
M
W
W
Q
Q
1210
|
L
I
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
A
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
R
N
N
F
F
T
T
1270
|
G
G
T
N
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
V
K
K
Q
Q
E
T
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
V
E
E
1300
|
S
S
M
I
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
I
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
I
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q202H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E11D+p.S17C+p.L68V+p.L101I+p.T124N+p.T125A+p.I135V+p.G140A+p.Q148R+p.D253E+p.V281M
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.975
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 2
TM score: 0.90394
Amino acid change:
E11D+S17C+L68V+L101I+T124N+T125A+I135V+G140A+Q148R+D253E+V281M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
D
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
C
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
V
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
N
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
V
K
K
Q
Q
E
E
F
F
G
A
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
R
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
E
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
M
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q200H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.K14R+p.V31I+p.T97A+p.L101I+p.T112V+p.S119R+p.T124A+p.T125S+p.G134N+p.K136T+p.N155H+p.V165I+p.V201I+p.T206S+p.Y227F+p.L234I+p.S255N+p.D256E+p.S283G
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.006
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.06
TM score: 0.94159
Amino acid change:
K14R+V31I+T97A+L101I+T112V+S119R+T124A+T125S+G134N+K136T+N155H+V165I+V201I+T206S+Y227F+L234I+S255N+D256E+S283G
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
R
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
A
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
V
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
R
N
N
F
F
T
T
1270
|
G
G
T
A
T
S
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
N
I
I
K
T
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
H
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
I
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
S
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
F
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
I
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
N
D
E
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
G
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q197H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.R20K+p.M50I+p.V77A+p.L101I+p.T112I+p.T124A+p.T125A+p.K136Q+p.G193E+p.V201I+p.T206S+p.T218L+p.I220V+p.L234V+p.D256E+p.R263K+p.D279G+p.S283G
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 75.488
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.49
TM score: 0.94371
Amino acid change:
S17N+R20K+M50I+V77A+L101I+T112I+T124A+T125A+K136Q+G193E+V201I+T206S+T218L+I220V+L234V+D256E+R263K+D279G+S283G
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
K
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
I
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
A
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
I
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
A
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
Q
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
E
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
S
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
L
K
K
I
V
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
V
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
E
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
K
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
G
C
C
V
V
A
A
1430
|
S
G
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q196H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E11D+p.R20K+p.E92Q+p.V201I+p.K211R+p.S230SN+p.D232E+p.D256E
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.87
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.22
TM score: 0.93275
Amino acid change:
E11D+R20K+E92Q+V201I+K211R+S230N+D232E+D256E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
D
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
K
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
Q
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
R
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
N
R
R
D
E
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
E
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q192H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.K14R+p.E69ED+p.E138K+p.G140S+p.Q148H+p.M154I+p.N155H+p.V201I
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.004
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.04
TM score: 0.94414
Amino acid change:
K14R+E69D+E138K+G140S+Q148H+M154I+N155H+V201I
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
R
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
D
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
K
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
V
E
E
1300
|
S
S
M
I
N
H
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q204H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [4]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.D25E+p.S119G+p.T122I+p.T124N+p.T125A+p.M154I+p.N155H+p.K156R+p.T206S+p.T218S
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.293
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.85
TM score: 0.95032
Amino acid change:
S17N+D25E+S119G+T122I+T124N+T125A+M154I+N155H+K156R+T206S+T218S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
E
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
G
N
N
F
F
T
I
1270
|
G
G
T
N
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
I
N
H
K
R
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
S
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
S
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Population sequencing of the integrase region assay
Experiment for
Drug Resistance		 TZM-bl cell line-based phenotypic assay
Mechanism Description In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q199H/k/R plus one to two additional INSTI mutations.
Key Molecule: HIV1 Integrase (HIV1 IT) [5]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.V32I+p.I36V+p.D41G+p.M50L+p.I72V+p.L101I+p.T124N+p.T125A+p.I135V+p.V201I+p.I208L+p.D256E
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 75.093
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.96
TM score: 0.94613
Amino acid change:
S17N+V32I+I36V+D41G+M50L+I72V+L101I+T124N+T125A+I135V+V201I+I208L+D256E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
I
1180
|
A
A
K
K
E
E
I
V
V
V
A
A
S
S
C
C
D
G
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
L
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
N
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
V
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
L
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
E
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 PCR; DNA sequencing assay
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Q148N, a novel integrase inhibitor resistance mutation associated with low-level reduction in elvitegravir susceptibility.
Key Molecule: HIV1 Integrase (HIV1 IT) [5]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.I72V+p.I113V+p.G140S+p.Q148H+p.V151I+p.L234V
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.388
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.87
TM score: 0.94681
Amino acid change:
I72V+I113V+G140S+Q148H+V151I+L234V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
V
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
I
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
V
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 PCR; DNA sequencing assay
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Q148N, a novel integrase inhibitor resistance mutation associated with low-level reduction in elvitegravir susceptibility.
Key Molecule: HIV1 Integrase (HIV1 IT) [6]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.I72V+p.I113V+p.V151I+p.L234V+p.R263K
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.989
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.79
TM score: 0.9494
Amino acid change:
I72V+I113V+V151I+L234V+R263K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
V
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
I
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
V
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
K
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Our results show that the R263k substitution decreased HIV-1 subtype C susceptibility to DTG and EVG by 3.3 and 50-fold, respectively. In subtype B, R263k conferred a somewhat lesser degree of drug resistance, that is, 2.1 and 25-fold decreases in susceptibility to DTG and EVG, respectively. R263k did not confer resistance against RAL in HIV-1 subtype C in accordance with results for subtype B.
Key Molecule: HIV1 Integrase (HIV1 IT) [6]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.K14R+p.D25E+p.V31I+p.L45S+p.I72V+p.E96D+p.F100Y+p.L101I+p.T112V+p.T124A+p.T125A+p.K136Q+p.V201I+p.K219N+p.N222K+p.L234I+p.R263K+p.A265V+p.R269K+p.D278A
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 72.767
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.45
TM score: 0.88138
Amino acid change:
K14R+D25E+V31I+L45S+I72V+E96D+F100Y+L101I+T112V+T124A+T125A+K136Q+V201I+K219N+N222K+L234I+R263K+A265V+R269K+D278A
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
R
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
E
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
S
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
D
T
T
A
A
Y
Y
F
Y
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
V
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
A
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
Q
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
N
I
I
Q
Q
N
K
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
I
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
K
K
K
A
V
K
K
I
I
I
I
R
K
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
A
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model TZM-bl cells Uterus Homo sapiens (Human) CVCL_B478
Experiment for
Molecule Alteration		 Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Our results show that the R263k substitution decreased HIV-1 subtype C susceptibility to DTG and EVG by 3.3 and 50-fold, respectively. In subtype B, R263k conferred a somewhat lesser degree of drug resistance, that is, 2.1 and 25-fold decreases in susceptibility to DTG and EVG, respectively. R263k did not confer resistance against RAL in HIV-1 subtype C in accordance with results for subtype B.
Key Molecule: HIV1 Integrase (HIV1 IT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.I72V+p.I113V+p.G118R+p.E138K+p.V151I+p.L234V
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.617
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.13
TM score: 0.94042
Amino acid change:
I72V+I113V+G118R+E138K+V151I+L234V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
V
H
H
T
T
D
D
N
N
G
R
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
K
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
I
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
V
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model BL21 cells Cerebrospinal fluid Homo sapiens (Human) CVCL_M639
Experiment for
Molecule Alteration		 Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Amino acid changes in IN may contribute to dolutegravir resistance or sensitivity.
Key Molecule: HIV1 Integrase (HIV1 IT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.I72V+p.I113V+p.G118R+p.V151I+p.L234V
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.287
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.9
TM score: 0.94661
Amino acid change:
I72V+I113V+G118R+V151I+L234V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
V
H
H
T
T
D
D
N
N
G
R
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
I
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
V
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model BL21 cells Cerebrospinal fluid Homo sapiens (Human) CVCL_M639
Experiment for
Molecule Alteration		 Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Amino acid changes in IN may contribute to dolutegravir resistance or sensitivity.
Key Molecule: HIV1 Integrase (HIV1 IT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.H51Y+p.I72V+p.I113V+p.V151I+p.L234V
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.892
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.82
TM score: 0.95
Amino acid change:
H51Y+I72V+I113V+V151I+L234V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
Y
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
V
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
I
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
V
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model BL21 cells Cerebrospinal fluid Homo sapiens (Human) CVCL_M639
Experiment for
Molecule Alteration		 Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Amino acid changes in IN may contribute to dolutegravir resistance or sensitivity.
Key Molecule: HIV1 Integrase (HIV1 IT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E11D+p.K14R+p.S24N+p.V31I+p.M50I+p.L74I+p.A91E+p.L101I+p.T112V+p.G118R+p.S119R+p.T124A+p.T125A+p.A133T+p.G134N+p.I135V+p.K136T+p.E138K+p.V165I+p.V201I+p.T206S+p.T218I+p.L234I+p.S283D
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.856
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.99
TM score: 0.94349
Amino acid change:
E11D+K14R+S24N+V31I+M50I+L74I+A91E+L101I+T112V+G118R+S119R+T124A+T125A+A133T+G134N+I135V+K136T+E138K+V165I+V201I+T206S+T218I+L234I+S283D
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
D
H
H
1160
|
E
E
K
R
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
N
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
I
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
I
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
E
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
V
1260
|
I
I
H
H
T
T
D
D
N
N
G
R
S
R
N
N
F
F
T
T
1270
|
G
G
T
A
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
T
G
N
I
V
K
T
Q
Q
E
K
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
I
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
S
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
I
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
I
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
D
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model BL21 cells Cerebrospinal fluid Homo sapiens (Human) CVCL_M639
Experiment for
Molecule Alteration		 Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Amino acid changes in IN may contribute to dolutegravir resistance or sensitivity.
Key Molecule: HIV1 Integrase (HIV1 IT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E11D+p.K14R+p.S24N+p.V31I+p.M50I+p.L74I+p.A91E+p.L101I+p.T112V+p.G118R+p.S119R+p.T124A+p.T125A+p.A133T+p.G134N+p.I135V+p.K136T+p.V165I+p.V201I+p.T206S+p.T218I+p.L234I+p.S283D
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.012
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.12
TM score: 0.87969
Amino acid change:
E11D+K14R+S24N+V31I+M50I+L74I+A91E+L101I+T112V+G118R+S119R+T124A+T125A+A133T+G134N+I135V+K136T+V165I+V201I+T206S+T218I+L234I+S283D
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
D
H
H
1160
|
E
E
K
R
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
N
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
I
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
I
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
E
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
V
1260
|
I
I
H
H
T
T
D
D
N
N
G
R
S
R
N
N
F
F
T
T
1270
|
G
G
T
A
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
T
G
N
I
V
K
T
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
I
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
S
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
I
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
I
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
D
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model BL21 cells Cerebrospinal fluid Homo sapiens (Human) CVCL_M639
Experiment for
Molecule Alteration		 Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Amino acid changes in IN may contribute to dolutegravir resistance or sensitivity.
Key Molecule: HIV1 Integrase (HIV1 IT) [3]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E11D+p.K14R+p.S24N+p.V31I+p.M50I+p.H51Y+p.L74I+p.A91E+p.L101I+p.T112V+p.S119R+p.T124A+p.T125A+p.A133T+p.G134N+p.I135V+p.K136T+p.V165I+p.V201I+p.T206S+p.T218I+p.L234I+p.S283D
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.056
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.03
TM score: 0.94126
Amino acid change:
E11D+K14R+S24N+V31I+M50I+H51Y+L74I+A91E+L101I+T112V+S119R+T124A+T125A+A133T+G134N+I135V+K136T+V165I+V201I+T206S+T218I+L234I+S283D
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
D
H
H
1160
|
E
E
K
R
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
N
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
I
H
Y
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
I
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
E
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
V
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
R
N
N
F
F
T
T
1270
|
G
G
T
A
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
T
G
N
I
V
K
T
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
I
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
S
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
I
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
I
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
D
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model BL21 cells Cerebrospinal fluid Homo sapiens (Human) CVCL_M639
Experiment for
Molecule Alteration		 Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Amino acid changes in IN may contribute to dolutegravir resistance or sensitivity.
Key Molecule: HIV1 Integrase (HIV1 IT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.R20K+p.V31I+p.L45I+p.L101I+p.I135IV+p.N155H+p.E157Q+p.K160Q+p.V201I+p.K215N+p.A265V
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.316
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.36
TM score: 0.93941
Amino acid change:
R20K+V31I+L45I+L101I+I135V+N155H+E157Q+K160Q+V201I+K215N+A265V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
K
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
I
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
V
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
H
K
K
E
Q
L
L
K
K
K
Q
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
N
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
V
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 RT-PCR; Sequencing assay
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Five mutations (A49P, L68FL, T97A, E138k and L234V) were implicated in emergent dolutegravir resistance, with a concomitant severe compromise in viral replicative capacity.
Key Molecule: HIV1 Integrase (HIV1 IT) [2]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.R20K+p.V31I+p.L45I+p.L101I+p.K111KR+p.I135IV+p.E157Q+p.K160Q+p.V201I+p.K215N+p.A265AV
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.2
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.19
TM score: 0.93297
Amino acid change:
R20K+V31I+L45I+L101I+K111R+I135V+E157Q+K160Q+V201I+K215N+A265V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
K
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
I
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
R
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
V
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
Q
L
L
K
K
K
Q
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
N
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
V
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 RT-PCR; Sequencing assay
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Five mutations (A49P, L68FL, T97A, E138k and L234V) were implicated in emergent dolutegravir resistance, with a concomitant severe compromise in viral replicative capacity.
Key Molecule: HIV1 Integrase (HIV1 IT) [7]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.L101I+p.T125A+p.I135V+p.D167DE+p.G193R+p.V201I+p.I208L+p.K211T+p.A265V+p.S283G
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.45
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.88
TM score: 0.9496
Amino acid change:
L101I+T125A+I135V+D167E+G193R+V201I+I208L+K211T+A265V+S283G
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
V
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
E
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
R
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
L
Q
Q
T
T
K
T
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
V
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
G
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model MT-2 cells Umbilical cord blood Homo sapiens (Human) CVCL_2631
MT-4 cells Umbilical cord blood Homo sapiens (Human) CVCL_2632
Experiment for
Molecule Alteration		 PCR; DNA sequencing assay
Experiment for
Drug Resistance		 PhenoSense assay
Mechanism Description Amino acid changes in IN may contribute to dolutegravir resistance or sensitivity.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.S24D+p.S39C+p.L45LQ+p.L101I+p.T124N+p.D167E+p.V201I+p.E212EA+p.R284RG+p.D286N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.411
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.67
TM score: 0.96515
Amino acid change:
S17N+S24D+S39C+L45Q+L101I+T124N+D167E+V201I+E212A+R284G+D286N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
D
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
C
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
Q
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
N
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
E
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
A
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
G
Q
Q
D
N
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S17N, S24D, S39C, L45LQ, L101I, T124N, D167E, V201I, E212EA, R284RG, D286N.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.D6E+p.E10D+p.V31I+p.L101I+p.T124A+p.K156N+p.V201I+p.V249VI+p.M275V
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.905
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.29
TM score: 0.95499
Amino acid change:
D6E+E10D+V31I+L101I+T124A+K156N+V201I+V249I+M275V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
E
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
N
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
I
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
V
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included D6E, E10D, V31I, L101I, T124A, K156N, V201I, V249VI, M275V.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.D6E+p.E10D+p.A23S+p.V31I+p.L101I+p.T124A+p.K156N+p.V201I+p.M275V
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.51
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 2
TM score: 0.93562
Amino acid change:
D6E+E10D+A23S+V31I+L101I+T124A+K156N+V201I+M275V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
E
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
S
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
N
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
V
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included D6E, E10D, A23S, V31I, L101I, T124A, K156N, V201I, M275V.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.I72V+p.L101I+p.G140S+p.Q148H+p.K156N+p.V201I+p.D207DG+p.I208L
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.664
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.58
TM score: 0.91726
Amino acid change:
S17N+I72V+L101I+G140S+Q148H+K156N+V201I+D207G+I208L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
N
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
G
I
L
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S17N, I72V, L101I, G140S, Q148H, K156N, V201I, D207DG, I208L.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.I72V+p.L101LI+p.K156N+p.V201I+p.I208L+p.R228RK+p.D286DN
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.454
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.74
TM score: 0.94594
Amino acid change:
S17N+I72V+L101I+K156N+V201I+I208L+R228K+D286N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
N
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
L
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
K
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
N
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S17N, I72V, L101LI, K156N, V201I, I208L, R228RK, D286DN.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.I72V+p.L101LI+p.E138EK+p.G140GS+p.Q148QH+p.K156N+p.V201I+p.I208L+p.D286DN
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.593
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.7
TM score: 0.91134
Amino acid change:
S17N+I72V+L101I+E138K+G140S+Q148H+K156N+V201I+I208L+D286N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
K
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
N
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
L
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
N
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S17N, I72V, L101LI, E138EK, G140GS, Q148QH, K156N, V201I, I208L, D286DN.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.K7R+p.S17N+p.V31I+p.T97A+p.L101I+p.T112A+p.T125A+p.Y143R+p.M154I+p.V201I
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.202
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.16
TM score: 0.9495
Amino acid change:
K7R+S17N+V31I+T97A+L101I+T112A+T125A+Y143R+M154I+V201I
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
R
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
A
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
A
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
R
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
I
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included K7R, S17N, V31I, T97A, L101I, T112A, T125A, Y143R, M154I, V201I.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.V31I+p.V79VI+p.L101I+p.I113IL+p.T124A+p.K211KR+p.L234I+p.A265AV
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.278
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.83
TM score: 0.9294
Amino acid change:
S17N+V31I+V79I+L101I+I113L+T124A+K211R+L234I+A265V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
I
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
L
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
R
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
I
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
V
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S17N, V31I, V79VI, L101I, I113IL, T124A, K211KR, L234I, A265AV.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.V31I+p.E92EQ+p.T97TA+p.L101I+p.T124A+p.Y143R+p.A169AG+p.L234I
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 71.838
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 3.35
TM score: 0.72372
Amino acid change:
S17N+V31I+E92Q+T97A+L101I+T124A+Y143R+A169G+L234I
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
Q
1240
|
T
T
G
G
Q
Q
E
E
T
A
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
R
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
G
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
I
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S17N, V31I, E92EQ, T97TA, L101I, T124A, Y143R, A169AG, L234I.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.I72V+p.A98AT+p.L101I+p.G140GS+p.Q148QH+p.K156KN+p.V201I+p.I208L+p.D286DN
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 72.705
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.79
TM score: 0.90093
Amino acid change:
S17N+I72V+A98T+L101I+G140S+Q148H+K156N+V201I+I208L+D286N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
T
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
N
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
L
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
N
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S17N, I72V, A98AT, L101I, G140GS, Q148QH, K156KN, V201I, I208L, D286DN.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10DG+p.E11D+p.V31I+p.S119P+p.T122I+p.T125A+p.V126M+p.A128AT+p.G140GS+p.V151VI+p.N155H+p.G163E+p.S195C+p.L234V+p.D279DN
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.524
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.29
TM score: 0.91732
Amino acid change:
E10DG+E11D+V31I+S119P+T122I+T125A+V126M+A128T+G140S+V151I+N155H+G163E+S195C+L234V+D279N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
D
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
P
N
N
F
F
T
I
1270
|
G
G
A
A
T
A
V
M
R
R
A
T
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
I
E
E
1300
|
S
S
M
M
N
H
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
E
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
C
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
V
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
N
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E10DG, E11D, V31I, S119P, T122I, T125A, V126M, A128AT, G140GS, V151VI, N155H, G163E, S195C, L234V, D279DN.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.D6E+p.E10D+p.A23S+p.V31I+p.L101I+p.T124A+p.V151I+p.N155H+p.K156N+p.V201I+p.D232N+p.M275V
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.069
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.11
TM score: 0.92216
Amino acid change:
D6E+E10D+A23S+V31I+L101I+T124A+V151I+N155H+K156N+V201I+D232N+M275V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
E
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
S
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
I
E
E
1300
|
S
S
M
M
N
H
K
N
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
V
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included D6E, E10D, A23S, V31I, L101I, T124A, V151I, N155H, K156N, V201I, D232N, M275V.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.I72V+p.L101LI+p.E138EK+p.G140GS+p.Q148QH+p.N155ND+p.K156KN+p.V201I+p.I208L+p.D256DE+p.D286DN
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.786
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.95
TM score: 0.94871
Amino acid change:
S17N+I72V+L101I+E138K+G140S+Q148H+N155D+K156N+V201I+I208L+D256E+D286N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
K
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
D
K
N
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
L
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
E
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
N
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S17N, I72V, L101LI, E138EK, G140GS, Q148QH, N155ND, K156KN, V201I, I208L, D256DE, D286DN.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.S24D+p.S39C+p.L45LQ+p.L101I+p.T124N+p.G140S+p.Q148H+p.D167E+p.V201I+p.E212A+p.R284G+p.D286N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.028
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.1
TM score: 0.94698
Amino acid change:
S17N+S24D+S39C+L45Q+L101I+T124N+G140S+Q148H+D167E+V201I+E212A+R284G+D286N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
D
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
C
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
Q
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
N
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
E
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
I
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
A
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
G
Q
Q
D
N
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S17N, S24D, S39C, L45LQ, L101I, T124N, G140S, Q148H, D167E, V201I, E212A, R284G, D286N.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.D25E+p.I72V+p.G140S+p.Q148H+p.V151I+p.K211R+p.K215N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.557
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.49
TM score: 0.95665
Amino acid change:
D25E+I72V+G140S+Q148H+V151I+K211R+K215N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
E
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
I
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
R
E
E
1360
|
L
L
Q
Q
K
N
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included D25E, I72V, G140S, Q148H, V151I, K211R, K215N.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.V31I+p.V79VI+p.E92EQ+p.L101I+p.T124A+p.G140GS+p.Q148QR+p.N155NH+p.L234I
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.317
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.82
TM score: 0.94992
Amino acid change:
S17N+V31I+V79I+E92Q+L101I+T124A+G140S+Q148R+N155H+L234I
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
I
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
I
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
Q
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
T
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
R
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
H
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
I
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S17N, V31I, V79VI, E92EQ, L101I, T124A, G140GS, Q148QR, N155NH, L234I.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.L63I+p.I73V+p.L74I+p.E96D+p.L101I+p.T112I+p.G140S+p.Q148H+p.I208L+p.D232E+p.L234LF
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 72.589
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.22
TM score: 0.97243
Amino acid change:
L63I+I73V+L74I+E96D+L101I+T112I+G140S+Q148H+I208L+D232E+L234F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
I
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
V
L
I
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
D
T
T
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
I
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
L
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
E
1380
|
P
P
L
F
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included L63I, I73V, L74I, E96D, L101I, T112I, G140S, Q148H, I208L, D232E, L234LF.
Key Molecule: HIV1 Integrase (HIV1 IT) [9]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.H51Y+p.I72V+p.I113V+p.L234V
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.6
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.59
TM score: 0.96441
Amino acid change:
H51Y+I72V+I113V+L234V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
Y
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
V
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
V
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included H51Y, I72V, I113V, L234V.
Key Molecule: HIV1 Integrase (HIV1 IT) [9]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.I72V+p.I113V+p.L234V+p.R263K
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 75.031
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.93
TM score: 0.94589
Amino acid change:
I72V+I113V+L234V+R263K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
V
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
V
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
K
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included I72V, I113V, L234V, R263K.
Key Molecule: HIV1 Integrase (HIV1 IT) [9]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.H51Y+p.I72V+p.I113V+p.L234V+p.R263K
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.331
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.22
TM score: 0.93927
Amino acid change:
H51Y+I72V+I113V+L234V+R263K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
Y
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
V
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
G
G
A
A
T
T
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
V
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
K
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included H51Y, I72V, I113V, L234V, R263K.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G4GR+p.R20K+p.T97A+p.T112V+p.I113V+p.T125A+p.Y143YC+p.H171Q+p.Y194YH+p.I200M+p.I203M+p.S230R
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included G4GR, R20K, T97A, T112V, I113V, T125A, Y143YC, H171Q, Y194YH, I200M, I203M, S230R.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.D6E+p.K14KR+p.S17N+p.R20K+p.D25E+p.S39C+p.L45X+p.T97TA+p.L101I+p.S119SR+p.T124A+p.V151VI+p.N155NH+p.K160T+p.G163GR+p.V201I+p.K211R+p.D288N
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included D6E, K14KR, S17N, R20K, D25E, S39C, L45X, T97TA, L101I, S119SR, T124A, V151VI, N155NH, K160T, G163GR, V201I, K211R, D288N.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S147G
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S147G.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E92G
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E92G.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q148R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Q148R.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T66I+p.N155H
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T66I, N155H.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.N155H
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included N155H.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E92Q
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E92Q.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Y143R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Y143R.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q148K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Q148K.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T66K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T66K.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.N155H
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included N155H.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E92Q+p.N155H
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E92Q, N155H.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E92Q
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E92Q.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E138K+p.Q148R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E138K, Q148R.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E92Q+p.N155H
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E92Q, N155H.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S153Y
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S153Y.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T66I+p.Q148R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T66I, Q148R.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G140S+p.Q148R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included G140S, Q148R.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G140S+p.Q148H
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included G140S, Q148H.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E92Q+p.Q148R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E92Q, Q148R.
Key Molecule: HIV1 Integrase (HIV1 IT) [10]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q148R+p.N155H
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Q148R, N155H.
Key Molecule: HIV1 Integrase (HIV1 IT) [8]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E138K+p.Q148K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E138K, Q148K.
Key Molecule: HIV1 Integrase (HIV1 IT) [11]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S17N+p.T97A+p.L101I+p.T112M+p.S119P+p.T122I+p.T124N+p.T125A+p.G140S+p.Q148H
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.611
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.43
TM score: 0.92578
Amino acid change:
S17N+T97A+L101I+T112M+S119P+T122I+T124N+T125A+G140S+Q148H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
D
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
N
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
A
A
A
Y
Y
F
F
L
I
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
M
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
P
N
N
F
F
T
I
1270
|
G
G
T
N
T
A
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S17N, T97A, L101I, T112M, S119P, T122I, T124N, T125A, G140S, Q148H.
Key Molecule: HIV1 Integrase (HIV1 IT) [11]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.D6DE+p.E11D+p.S17T+p.A23V+p.V37I+p.I60IM+p.K71Q+p.A91AS+p.T97A+p.K111A+p.S119R+p.T124TN+p.T125Q+p.E138T+p.G140S+p.Q148H+p.I203M
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.688
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.04
TM score: 0.87203
Amino acid change:
D6E+E11D+S17T+A23V+V37I+I60M+K71Q+A91S+T97A+K111A+S119R+T124N+T125Q+E138T+G140S+Q148H+I203M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
E
K
K
A
A
Q
Q
D
D
E
D
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
T
N
N
W
W
R
R
A
A
M
M
1170
|
A
V
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
I
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
M
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
Q
V
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
S
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
A
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
A
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
R
N
N
F
F
T
T
1270
|
G
G
T
N
T
Q
V
V
R
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
T
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
M
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
N
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included D6DE, E11D, S17T, A23V, V37I, I60IM, K71Q, A91AS, T97A, K111A, S119R, T124TN, T125Q, E138T, G140S, Q148H, I203M.
Key Molecule: HIV1 Integrase (HIV1 IT) [12]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T122I
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T122I.
Key Molecule: HIV1 Integrase (HIV1 IT) [12]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.L74I
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included L74I.
Key Molecule: HIV1 Integrase (HIV1 IT) [12]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.NULL
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included NULL.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T66I+p.Q148K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T66I, Q148K.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S147G
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S147G.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S153A
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S153A.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S119T
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S119T.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q95R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Q95R.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E92G
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E92G.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E170A
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E170A.
Key Molecule: HIV1 Integrase (HIV1 IT) [12]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S119R+p.F121Y
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S119R, F121Y.
Key Molecule: HIV1 Integrase (HIV1 IT) [12]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T122I
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T122I.
Key Molecule: HIV1 Integrase (HIV1 IT) [12]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T97A+p.S119R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T97A, S119R.
Key Molecule: HIV1 Integrase (HIV1 IT) [12]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G70R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included G70R.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.I72A+p.N155H
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included I72A, N155H.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S147G
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S147G.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S153F
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S153F.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S119R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S119R.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.M50I
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included M50I.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.A128T
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included A128T.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G163R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included G163R.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q95K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Q95K.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E157Q
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E157Q.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q148R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Q148R.
Key Molecule: HIV1 Integrase (HIV1 IT) [12]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T97A+p.G163R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T97A, G163R.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.N155H
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included N155H.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S153Y
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S153Y.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.L234F
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included L234F.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.H51Y
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included H51Y.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T66I+p.R263K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T66I, R263K.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E92Q
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E92Q.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E92Q
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E92Q.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.N155H
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included N155H.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Y143R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Y143R.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q146L
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Q146L.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q146R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Q146R.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.R263K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included R263K.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S24G+p.N155H+p.D253E
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S24G, N155H, D253E.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.L45Q+p.T115H
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included L45Q, T115H.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q148K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Q148K.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.V151L
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included V151L.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E157K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E157K.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E138K+p.Q148R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E138K, Q148R.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S153Y
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S153Y.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.R263K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included R263K.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T66K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T66K.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S153Y+p.L234F
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S153Y, L234F.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S153F
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S153F.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S153Y
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included S153Y.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q148R+p.N155H
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Q148R, N155H.
Key Molecule: HIV1 Integrase (HIV1 IT) [14]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q146I
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included Q146I.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E92Q+p.G140A
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E92Q, G140A.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G140A+p.Q148R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included G140A, Q148R.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E138K+p.Q148K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E138K, Q148K.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T66I+p.E138K+p.Q148R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T66I, E138K, Q148R.
Key Molecule: HIV1 Integrase (HIV1 IT) [12]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G118R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included G118R.
Key Molecule: HIV1 Integrase (HIV1 IT) [12]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T97A+p.G118R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T97A, G118R.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E138K+p.G140A+p.Q148R
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included E138K, G140A, Q148R.
Key Molecule: HIV1 Integrase (HIV1 IT) [13]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T66I+p.E138K+p.Q148K
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration		 Sanger sequencing assay; GeneSeq assay; Population sequencing of the integrase region assay; DNA sequencing assay; Site-directed mutagenesis
Experiment for
Drug Resistance		 PhenoSense assay; Viral load assay; A single-cycle assay; TZM-bl cell line-based phenotypic assay; SDMs and phenotyping assay
Mechanism Description Some mutations identified were assiacted with resistance in the HIV isolates, those mutations included T66I, E138K, Q148K.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.S123G+p.T124A+p.K127R+p.G140S+p.Q148H+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 73.626
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.91
TM score: 0.9455
Amino acid change:
E10D+I72V+S123G+T124A+K127R+G140S+Q148H+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
H
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E295Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.S123G+p.T124A+p.K127R+p.G140S+p.Q148R+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.84
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.93
TM score: 0.94573
Amino acid change:
E10D+I72V+S123G+T124A+K127R+G140S+Q148R+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
S
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
R
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E294Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.S123G+p.T124A+p.K127R+p.N155H+p.E157Q+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.646
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.84
TM score: 0.94985
Amino acid change:
E10D+I72V+S123G+T124A+K127R+N155H+E157Q+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
H
K
K
E
Q
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E288Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.S119P+p.S123G+p.T124A+p.K127R+p.N155H+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.882
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.1
TM score: 0.88224
Amino acid change:
E10D+I72V+S119P+S123G+T124A+K127R+N155H+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
P
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
H
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E285Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.M50I+p.I72V+p.S123G+p.T124A+p.K127R+p.N155H+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.803
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1
TM score: 0.94631
Amino acid change:
E10D+M50I+I72V+S123G+T124A+K127R+N155H+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
I
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
H
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E282Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.S123G+p.T124A+p.K127R+p.Q148R+p.E157Q+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.431
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.8
TM score: 0.95061
Amino acid change:
E10D+I72V+S123G+T124A+K127R+Q148R+E157Q+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
R
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
Q
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E258Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.S119P+p.S123G+p.T124A+p.K127R+p.Q148R+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.614
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.81
TM score: 0.95013
Amino acid change:
E10D+I72V+S119P+S123G+T124A+K127R+Q148R+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
P
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
R
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E257Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.M50I+p.I72V+p.S123G+p.T124A+p.K127R+p.Q148R+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.988
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.83
TM score: 0.9497
Amino acid change:
E10D+M50I+I72V+S123G+T124A+K127R+Q148R+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
I
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
R
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E250Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.S123G+p.T124A+p.K127R+p.S147G+p.E157Q+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.081
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.77
TM score: 0.95113
Amino acid change:
E10D+I72V+S123G+T124A+K127R+S147G+E157Q+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
G
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
Q
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E280Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.S119P+p.S123G+p.T124A+p.K127R+p.S147G+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.949
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.81
TM score: 0.95024
Amino acid change:
E10D+I72V+S119P+S123G+T124A+K127R+S147G+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
P
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
G
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E262Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.M50I+p.I72V+p.S123G+p.T124A+p.K127R+p.S147G+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.838
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.81
TM score: 0.94952
Amino acid change:
E10D+M50I+I72V+S123G+T124A+K127R+S147G+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
I
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
G
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E274Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.E92Q+p.S123G+p.T124A+p.K127R+p.E157Q+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.844
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.89
TM score: 0.94783
Amino acid change:
E10D+I72V+E92Q+S123G+T124A+K127R+E157Q+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
Q
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
Q
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E289Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.E92Q+p.S119P+p.S123G+p.T124A+p.K127R+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.952
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.97
TM score: 0.94406
Amino acid change:
E10D+I72V+E92Q+S119P+S123G+T124A+K127R+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
Q
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
P
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E281Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.M50I+p.I72V+p.E92Q+p.S123G+p.T124A+p.K127R+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 75.419
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.11
TM score: 0.94131
Amino acid change:
E10D+M50I+I72V+E92Q+S123G+T124A+K127R+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
I
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
Q
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E276Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.T66I+p.I72V+p.S123G+p.T124A+p.K127R+p.E157Q+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 75.098
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.86
TM score: 0.94926
Amino acid change:
E10D+T66I+I72V+S123G+T124A+K127R+E157Q+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
I
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
Q
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E232Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.T66I+p.I72V+p.S119P+p.S123G+p.T124A+p.K127R+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 75.357
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.89
TM score: 0.94778
Amino acid change:
E10D+T66I+I72V+S119P+S123G+T124A+K127R+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
I
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
P
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E228Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.M50I+p.T66I+p.I72V+p.S123G+p.T124A+p.K127R+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 75.344
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.9
TM score: 0.94725
Amino acid change:
E10D+M50I+T66I+I72V+S123G+T124A+K127R+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
I
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
I
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E231Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.S123G+p.T124A+p.K127R+p.E170A+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.934
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.92
TM score: 0.9467
Amino acid change:
E10D+I72V+S123G+T124A+K127R+E170A+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
G
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
A
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E270Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
Key Molecule: HIV1 Integrase (HIV1 IT) [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E10D+p.I72V+p.S123G+p.T124A+p.K127R+p.G163K+p.D232N
 Molecule Info 
Wild Type Structure Method: AlphaFold  Average pLDDT: 75.736
Click to Show/Hide The PAE Picture
Mutant Type Structure Method: AlphaFold  Average pLDDT: 74.915
Click to Show/Hide The PAE Picture
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.88
TM score: 0.94863
Amino acid change:
E10D+I72V+S123G+T124A+K127R+G163K+D232N
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
F
F
L
L
1150
|
D
D
G
G
I
I
D
D
K
K
A
A
Q
Q
E
D
E
E
H
H
1160
|
E
E
K
K
Y
Y
H
H
S
S
N
N
W
W
R
R
A
A
M
M
1170
|
A
A
S
S
D
D
F
F
N
N
L
L
P
P
P
P
V
V
V
V
1180
|
A
A
K
K
E
E
I
I
V
V
A
A
S
S
C
C
D
D
K
K
1190
|
C
C
Q
Q
L
L
K
K
G
G
E
E
A
A
M
M
H
H
G
G
1200
|
Q
Q
V
V
D
D
C
C
S
S
P
P
G
G
I
I
W
W
Q
Q
1210
|
L
L
D
D
C
C
T
T
H
H
L
L
E
E
G
G
K
K
I
V
1220
|
I
I
L
L
V
V
A
A
V
V
H
H
V
V
A
A
S
S
G
G
1230
|
Y
Y
I
I
E
E
A
A
E
E
V
V
I
I
P
P
A
A
E
E
1240
|
T
T
G
G
Q
Q
E
E
T
T
A
A
Y
Y
F
F
L
L
L
L
1250
|
K
K
L
L
A
A
G
G
R
R
W
W
P
P
V
V
K
K
T
T
1260
|
I
I
H
H
T
T
D
D
N
N
G
G
S
S
N
N
F
F
T
T
1270
|
S
G
T
A
T
T
V
V
K
R
A
A
A
A
C
C
W
W
W
W
1280
|
A
A
G
G
I
I
K
K
Q
Q
E
E
F
F
G
G
I
I
P
P
1290
|
Y
Y
N
N
P
P
Q
Q
S
S
Q
Q
G
G
V
V
V
V
E
E
1300
|
S
S
M
M
N
N
K
K
E
E
L
L
K
K
K
K
I
I
I
I
1310
|
G
K
Q
Q
V
V
R
R
D
D
Q
Q
A
A
E
E
H
H
L
L
1320
|
K
K
T
T
A
A
V
V
Q
Q
M
M
A
A
V
V
F
F
I
I
1330
|
H
H
N
N
F
F
K
K
R
R
K
K
G
G
G
G
I
I
G
G
1340
|
G
G
Y
Y
S
S
A
A
G
G
E
E
R
R
I
I
V
V
D
D
1350
|
I
I
I
I
A
A
T
T
D
D
I
I
Q
Q
T
T
K
K
E
E
1360
|
L
L
Q
Q
K
K
Q
Q
I
I
T
T
K
K
I
I
Q
Q
N
N
1370
|
F
F
R
R
V
V
Y
Y
Y
Y
R
R
D
D
S
S
R
R
D
N
1380
|
P
P
L
L
W
W
K
K
G
G
P
P
A
A
K
K
L
L
L
L
1390
|
W
W
K
K
G
G
E
E
G
G
A
A
V
V
V
V
I
I
Q
Q
1400
|
D
D
N
N
S
S
D
D
I
I
K
K
V
V
V
V
P
P
R
R
1410
|
R
R
K
K
A
A
K
K
I
I
I
I
R
R
D
D
Y
Y
G
G
1420
|
K
K
Q
Q
M
M
A
A
G
G
D
D
D
D
C
C
V
V
A
A
1430
|
S
S
R
R
Q
Q
D
D
E
E
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 IN sequencing assay
Experiment for
Drug Resistance		 SDMs and phenotyping assay
Mechanism Description Total 6 of 39 minor INSTI-R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN-treatment-na ve subjects with no impact on INSTI susceptibility. When each combined with major INSTI-R mutation, M50I, S119P, and E256Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.
References
Ref 1 Antiviral activity of HIV-1 integrase strand-transfer inhibitors against mutants with integrase resistance-associated mutations and their frequency in treatment-na ve individuals. J Med Virol. 2019 Dec;91(12):2188-2194. doi: 10.1002/jmv.25564. Epub 2019 Aug 20.
Ref 2 Evolution of a novel pathway leading to dolutegravir resistance in a patient harbouring N155H and multiclass drug resistance. J Antimicrob Chemother. 2015 Feb;70(2):405-11. doi: 10.1093/jac/dku387. Epub 2014 Oct 3.
Ref 3 Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. J Virol. 2015 Mar;89(6):3163-75. doi: 10.1128/JVI.03353-14. Epub 2014 Dec 31.
Ref 4 Comparable In Vitro Activities of Second-Generation HIV-1 Integrase Strand Transfer Inhibitors (INSTIs) on HIV-1 Clinical Isolates with INSTI Resistance Mutations. Antimicrob Agents Chemother. 2019 Dec 20;64(1):e01717-19. doi: 10.1128/AAC.01717-19. Print 2019 Dec 20.
Ref 5 Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility. AIDS Res Hum Retroviruses. 2016 Jul;32(7):702-4. doi: 10.1089/AID.2016.0038. Epub 2016 Apr 19.
Ref 6 The R263K substitution in HIV-1 subtype C is more deleterious for integrase enzymatic function and viral replication than in subtype B. AIDS. 2015 Jul 31;29(12):1459-66. doi: 10.1097/QAD.0000000000000752.
Ref 7 Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Antimicrob Agents Chemother. 2016 Nov 21;60(12):7086-7097. doi: 10.1128/AAC.01474-16. Print 2016 Dec.
Ref 8 The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adultsJ Acquir Immune Defic Syndr. 2012 Nov 1;61(3):297-301. doi: 10.1097/QAI.0b013e31826bfd02.
Ref 9 Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressureRetrovirology. 2013 Feb 22;10:22. doi: 10.1186/1742-4690-10-22.
Ref 10 Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitnessAntimicrob Agents Chemother. 2013 Jun;57(6):2654-63. doi: 10.1128/AAC.02568-12. Epub 2013 Mar 25.
Ref 11 Rapid development of high level resistance to dolutegravir with emergence of T97A mutation in two treatment experienced individuals with baseline partial sensitivity to dolutegravir.
Ref 12 Bictegravir Resistance Profile: Data for External Experts.
Ref 13 Integrase Inhibitor Resistance Selections Initiated with Drug Resistant HIV-1.
Ref 14 Pre-existing HIV-1 integrase polymorphisms do not impact treatment response to elvitegravir-containing fixed-dose combination regimens in treatment-naive patients.

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Yu.