Disease Information

General Information of the Disease (ID: DIS00558)

• Name: HIV infection
• ICD: ICD-11: 1C62

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Amprenavir

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: OTU domain-containing protein 4 (OTUD4) [1]

• Resistant Disease: acquired immunodeficiency syndrome [ICD-11: 1C62.3Z]
• Resistant Drug: Amprenavir
• Molecule Alteration: Mutation; Interaction
• Mechanism Description: Binding free energies calculated by MM-GBSA method suggest that the decrease in binding enthalpy and the increase in binding entropy induced by mutations V32I, I50V and I84V are responsible for drug resistance of the mutated PRs on APV. The energetic contributions of separate residues on binding of APV to the PR show that V32I, I50V and I84V highly disturb the interactions of two flaps with APV and mostly drive the decrease in binding ability of APV to the PR. Thus, the conformational changes of two flaps in the PR caused by V32I, I50V and I84V play key roles in drug resistance of three mutated PR towards APV.

Key Molecule: OTU domain-containing protein 4 (OTUD4) [1]

• Resistant Disease: acquired immunodeficiency syndrome [ICD-11: 1C62.3Z]
• Resistant Drug: Amprenavir
• Molecule Alteration: Mutation; K103N + V106M
• Mechanism Description: Binding free energies calculated by MM-GBSA method suggest that the decrease in binding enthalpy and the increase in binding entropy induced by mutations V32I, I50V and I84V are responsible for drug resistance of the mutated PRs on APV. The energetic contributions of separate residues on binding of APV to the PR show that V32I, I50V and I84V highly disturb the interactions of two flaps with APV and mostly drive the decrease in binding ability of APV to the PR. Thus, the conformational changes of two flaps in the PR caused by V32I, I50V and I84V play key roles in drug resistance of three mutated PR towards APV.

Key Molecule: OTU domain-containing protein 4 (OTUD4) [1]

• Resistant Disease: acquired immunodeficiency syndrome [ICD-11: 1C62.3Z]
• Resistant Drug: Amprenavir
• Molecule Alteration: Mutation; K114N
• Mechanism Description: Binding free energies calculated by MM-GBSA method suggest that the decrease in binding enthalpy and the increase in binding entropy induced by mutations V32I, I50V and I84V are responsible for drug resistance of the mutated PRs on APV. The energetic contributions of separate residues on binding of APV to the PR show that V32I, I50V and I84V highly disturb the interactions of two flaps with APV and mostly drive the decrease in binding ability of APV to the PR. Thus, the conformational changes of two flaps in the PR caused by V32I, I50V and I84V play key roles in drug resistance of three mutated PR towards APV.

References

• Ref 1: Decoding drug resistant mechanism of V32I, I50V and I84V mutations of HIV-1 protease on amprenavir binding by using molecular dynamics simulations and MM-GBSA calculations. SAR QSAR Environ Res. 2022 Oct;33(10):805-831.