Amprenavir (ID: DG00576) Resistance Data of HIV
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: HIV1 Reverse transcriptase (HIV1 RT)
Resistant Disease Human immunodeficiency virus infection [ICD-11: 1C62.0]
Molecule Alteration
Alteration Patterns Alteration Types Resistance Mutation Total Point Scores Levels of Drug resistance base on the total point score Ref
p.G48T+p.L89M
Mutation N.A. Resistance [1]
Resistant Drug Amprenavir
Experimental Note Discovered Using In-vivo Testing Model
Experiment for
Molecule Alteration
Molecular dynamics simulation assay
Mechanism Description The decrease in van der Waals interactions of inhibitors with the mutated PR relative to the wild-type (WT) PR mostly drives the drug resistance of mutations toward these four inhibitors. The energy decomposition analysis further indicates that the drug resistance of mutations can be mainly attributed to the change in van der Waals and electrostatic energy of some key residues (around Ala28/Ala28' and Ile50/Ile50'). Our work can give significant guidance to design a new generation of anti-AIDS inhibitors targeting PR in the therapy of patients with HIV-1 infection.
References
Ref 1 Revealing the binding and drug resistance mechanism of amprenavir, indinavir, ritonavir, and nelfinavir complexed with HIV-1 protease due to double mutations G48T/L89M by molecular dynamics simulations and free energy analyses .Phys Chem Chem Phys. 2020 Feb 26;22(8):4464-4480. doi: 10.1039/c9cp06657h. 10.1039/c9cp06657h

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