Molecule Information

General Information of the Molecule (ID: Mol04239)
Name
Reverse transcriptase (RT) ,Human immunodeficiency virus
Synonyms
Reverse transcriptase (RT)
    Click to Show/Hide
Molecule Type
Protein
        Click to Show/Hide the Complete Species Lineage
Kingdom: Pararnavirae
Phylum: Artverviricota
Class: Revtraviricetes
Order: Ortervirales
Family: Retroviridae
Genus: Lentivirus
Species: Human immunodeficiency virus 1
Type(s) of Resistant Mechanism of This Molecule
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
MK-1439
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Resistant Drug MK-1439
 Drug Info 
Molecule Alteration Mutation
A2064C
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DS9 cells N.A. Homo sapiens (Human) N.A.
LTNP5 cells N.A. Homo sapiens (Human) N.A.
SM-1 cells N.A. Homo sapiens (Human) CVCL_IU19
SM2 cells N.A. Homo sapiens (Human) N.A.
CM-9 cells N.A. Homo sapiens (Human) CVCL_Y624
DU151 cells Prostate Homo sapiens (Human) N.A.
DU178 cells Prostate Homo sapiens (Human) N.A.
DU422 cells Prostate Homo sapiens (Human) N.A.
Experiment for
Drug Resistance		 In vitro phenotypic DOR susceptibility testing
Mechanism Description This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in HIV-1 subtype C. Prevalent drug resistance mutations were identified from a South African genotypic drug resistance testing database. Mutations, single or in combination, were introduced into replication-defective pseudoviruses and assessed for DOR susceptibility in vitro. The single V106M and Y188L mutations caused high-level resistance while others did not significantly impact DOR susceptibility. We observed an agreement between our in vitro and the Stanford HIVdb predicted susceptibilities. However, the F227L mutation was predicted to cause high-level DOR resistance but was susceptible in vitro. Combinations of mutations containing K103N, V106M or Y191L caused high-level resistance, in agreement with the predictions.
Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Resistant Drug MK-1439
 Drug Info 
Molecule Alteration Mutation
K344R
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DS9 cells N.A. Homo sapiens (Human) N.A.
LTNP5 cells N.A. Homo sapiens (Human) N.A.
SM-1 cells N.A. Homo sapiens (Human) CVCL_IU19
SM2 cells N.A. Homo sapiens (Human) N.A.
CM-9 cells N.A. Homo sapiens (Human) CVCL_Y624
DU151 cells Prostate Homo sapiens (Human) N.A.
DU178 cells Prostate Homo sapiens (Human) N.A.
DU422 cells Prostate Homo sapiens (Human) N.A.
Experiment for
Drug Resistance		 In vitro phenotypic DOR susceptibility testing
Mechanism Description This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in HIV-1 subtype C. Prevalent drug resistance mutations were identified from a South African genotypic drug resistance testing database. Mutations, single or in combination, were introduced into replication-defective pseudoviruses and assessed for DOR susceptibility in vitro. The single V106M and Y188L mutations caused high-level resistance while others did not significantly impact DOR susceptibility. We observed an agreement between our in vitro and the Stanford HIVdb predicted susceptibilities. However, the F227L mutation was predicted to cause high-level DOR resistance but was susceptible in vitro. Combinations of mutations containing K103N, V106M or Y193L caused high-level resistance, in agreement with the predictions.
Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Resistant Drug MK-1439
 Drug Info 
Molecule Alteration Mutation
L2003M
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DS9 cells N.A. Homo sapiens (Human) N.A.
LTNP5 cells N.A. Homo sapiens (Human) N.A.
SM-1 cells N.A. Homo sapiens (Human) CVCL_IU19
SM2 cells N.A. Homo sapiens (Human) N.A.
CM-9 cells N.A. Homo sapiens (Human) CVCL_Y624
DU151 cells Prostate Homo sapiens (Human) N.A.
DU178 cells Prostate Homo sapiens (Human) N.A.
DU422 cells Prostate Homo sapiens (Human) N.A.
Experiment for
Drug Resistance		 In vitro phenotypic DOR susceptibility testing
Mechanism Description This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in HIV-1 subtype C. Prevalent drug resistance mutations were identified from a South African genotypic drug resistance testing database. Mutations, single or in combination, were introduced into replication-defective pseudoviruses and assessed for DOR susceptibility in vitro. The single V106M and Y188L mutations caused high-level resistance while others did not significantly impact DOR susceptibility. We observed an agreement between our in vitro and the Stanford HIVdb predicted susceptibilities. However, the F227L mutation was predicted to cause high-level DOR resistance but was susceptible in vitro. Combinations of mutations containing K103N, V106M or Y192L caused high-level resistance, in agreement with the predictions.
Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Resistant Drug MK-1439
 Drug Info 
Molecule Alteration Mutation
V106M
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DS9 cells N.A. Homo sapiens (Human) N.A.
LTNP5 cells N.A. Homo sapiens (Human) N.A.
SM-1 cells N.A. Homo sapiens (Human) CVCL_IU19
SM2 cells N.A. Homo sapiens (Human) N.A.
CM-9 cells N.A. Homo sapiens (Human) CVCL_Y624
DU151 cells Prostate Homo sapiens (Human) N.A.
DU178 cells Prostate Homo sapiens (Human) N.A.
DU422 cells Prostate Homo sapiens (Human) N.A.
Experiment for
Drug Resistance		 In vitro phenotypic DOR susceptibility testing
Mechanism Description This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in HIV-1 subtype C. Prevalent drug resistance mutations were identified from a South African genotypic drug resistance testing database. Mutations, single or in combination, were introduced into replication-defective pseudoviruses and assessed for DOR susceptibility in vitro. The single V106M and Y188L mutations caused high-level resistance while others did not significantly impact DOR susceptibility. We observed an agreement between our in vitro and the Stanford HIVdb predicted susceptibilities. However, the F227L mutation was predicted to cause high-level DOR resistance but was susceptible in vitro. Combinations of mutations containing K103N, V106M or Y188L caused high-level resistance, in agreement with the predictions.
Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Resistant Drug MK-1439
 Drug Info 
Molecule Alteration Mutation
Y188L
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DS9 cells N.A. Homo sapiens (Human) N.A.
LTNP5 cells N.A. Homo sapiens (Human) N.A.
SM-1 cells N.A. Homo sapiens (Human) CVCL_IU19
SM2 cells N.A. Homo sapiens (Human) N.A.
CM-9 cells N.A. Homo sapiens (Human) CVCL_Y624
DU151 cells Prostate Homo sapiens (Human) N.A.
DU178 cells Prostate Homo sapiens (Human) N.A.
DU422 cells Prostate Homo sapiens (Human) N.A.
Experiment for
Drug Resistance		 In vitro phenotypic DOR susceptibility testing
Mechanism Description This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in HIV-1 subtype C. Prevalent drug resistance mutations were identified from a South African genotypic drug resistance testing database. Mutations, single or in combination, were introduced into replication-defective pseudoviruses and assessed for DOR susceptibility in vitro. The single V106M and Y188L mutations caused high-level resistance while others did not significantly impact DOR susceptibility. We observed an agreement between our in vitro and the Stanford HIVdb predicted susceptibilities. However, the F227L mutation was predicted to cause high-level DOR resistance but was susceptible in vitro. Combinations of mutations containing K103N, V106M or Y189L caused high-level resistance, in agreement with the predictions.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]
Sensitive Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
 Disease Info 
Sensitive Drug MK-1439
 Drug Info 
Molecule Alteration Mutation
F227L
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DS9 cells N.A. Homo sapiens (Human) N.A.
LTNP5 cells N.A. Homo sapiens (Human) N.A.
SM-1 cells N.A. Homo sapiens (Human) CVCL_IU19
SM2 cells N.A. Homo sapiens (Human) N.A.
CM-9 cells N.A. Homo sapiens (Human) CVCL_Y624
DU151 cells Prostate Homo sapiens (Human) N.A.
DU178 cells Prostate Homo sapiens (Human) N.A.
DU422 cells Prostate Homo sapiens (Human) N.A.
Experiment for
Drug Resistance		 In vitro phenotypic DOR susceptibility testing
Mechanism Description This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in HIV-1 subtype C. Prevalent drug resistance mutations were identified from a South African genotypic drug resistance testing database. Mutations, single or in combination, were introduced into replication-defective pseudoviruses and assessed for DOR susceptibility in vitro. The single V106M and Y188L mutations caused high-level resistance while others did not significantly impact DOR susceptibility. We observed an agreement between our in vitro and the Stanford HIVdb predicted susceptibilities. However, the F227L mutation was predicted to cause high-level DOR resistance but was susceptible in vitro. Combinations of mutations containing K103N, V106M or Y190L caused high-level resistance, in agreement with the predictions.
References
Ref 1 K103N, V106M and Y188L Significantly Reduce HIV-1 Subtype C Phenotypic Susceptibility to Doravirine. Viruses. 2024 Sep 20;16(9):1493.

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