Molecule Information

General Information of the Molecule (ID: Mol00970)

• Name: HIV2 Protease (HIV2 PR) ,Human immunodeficiency virus type 2
• Synonyms: Pr160Gag-Pol; MA; CA; SP1; p2; NC; TF; p6*; PR; Retropepsin; Exoribonuclease H; p66 RT; IN
• Molecule Type: Protein
• Gene Name: gag-pol
• Gene ID: 1490001
• Sequence:
  PQFSLWRRPVVKACIEGQSVEVLLDTGVDDSIVAGIELGSNYTPKIVGGIGGFINTKEYK
  DVEIEVVGKRVRATIMTGDTPINIFGRNILNTLGMTLNF
• Function: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins
• Uniprot ID: POL_HV2D2 (513-611)

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

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 5 drug(s) in total

Atazanavir

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Atazanavir
• Molecule Alteration: Missense mutation; p.I32V+p.V47I+p.M76L+p.I82V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Atazanavir
• Molecule Alteration: Missense mutation; p.I82V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Atazanavir
• Molecule Alteration: Missense mutation; p.M76L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Atazanavir
• Molecule Alteration: Missense mutation; p.V47I
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Atazanavir
• Molecule Alteration: Missense mutation; p.I32V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Darunavir

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Darunavir
• Molecule Alteration: Missense mutation; p.I32V+p.V47I+p.M76L+p.I82V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Darunavir
• Molecule Alteration: Missense mutation; p.I82V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Darunavir
• Molecule Alteration: Missense mutation; p.M76L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Darunavir
• Molecule Alteration: Missense mutation; p.V47I
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Darunavir
• Molecule Alteration: Missense mutation; p.I32V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Lopinavir

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Lopinavir
• Molecule Alteration: Missense mutation; p.I32V+p.V47I+p.M76L+p.I82V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Lopinavir
• Molecule Alteration: Missense mutation; p.I82V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Lopinavir
• Molecule Alteration: Missense mutation; p.M76L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Lopinavir
• Molecule Alteration: Missense mutation; p.V47I
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Lopinavir
• Molecule Alteration: Missense mutation; p.I32V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Saquinavir

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Saquinavir
• Molecule Alteration: Missense mutation; p.I32V+p.V47I+p.M76L+p.I82V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Saquinavir
• Molecule Alteration: Missense mutation; p.I82V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Saquinavir
• Molecule Alteration: Missense mutation; p.M76L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Saquinavir
• Molecule Alteration: Missense mutation; p.V47I
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Disease Class: Human immunodeficiency virus infection [ICD-11: 1C62.0] [1]

• Sensitive Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Sensitive Drug: Saquinavir
• Molecule Alteration: Missense mutation; p.I32V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T/17 cells; Kidney; Homo sapiens (Human); CVCL_1926
• Experiment for Molecule Alteration: Site-directed mutagenesis
• Experiment for Drug Resistance: PhenoSense assay; A single-cycle assay
• Mechanism Description: Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRdeta4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI.

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Glioblastoma [ICD-11: 2A00.02] [2]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: 8-week-old CAnN.Cg-Foxn1nu/CrlBltw (BALB/c nude) male mice, with U87MG-R cells; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay; Tumor weight assay
• Mechanism Description: Sp1-regulated PGE2 production activates FAO and TCA cycle in mitochondria, through EP1 and EP3 receptors, resulting in TMZ resistance in GBM. These results will provide us a new strategy to attenuate drug resistance or to re-sensitize recurred GBM.

References

• Ref 1: Four Amino Acid Changes in HIV-2 Protease Confer Class-Wide Sensitivity to Protease Inhibitors. J Virol. 2015 Nov 11;90(2):1062-9. doi: 10.1128/JVI.01772-15. Print 2016 Jan 15.
• Ref 2: Reprogramming of arachidonate metabolism confers temozolomide resistance to glioblastoma through enhancing mitochondrial activity in fatty acid oxidation. J Biomed Sci. 2022 Mar 25;29(1):21.