Abstract
Amprenavir is an HIV-1 protease inhibitor (PI) that has recently been approved for the treatment HIV/AIDS. Despite its outstanding safety and efficacy, site-specific mutations occurring at one or more residues in HIV-1 protease have caused the development of resistance to PI. Unfortunately, a comprehensive understanding of the resistance mechanisms is still lacking. Therefore, the present investigation aims to uncover the mechanism behind the resistance for amprenavir to HIV-1 protease triple mutant (V32I, I47V and V82I) by computational techniques. We have also highlighted the effect of mutations on the binding site residues and flap comprising residues in the HIV-1 protease by means of flexibility analysis. Molecular dockings were performed to gain insights into the binding mode of the amprenavir with HIV-1 protease structure. Subsequently, the docking results were also validated by means of PEARLS program. The obtained results provide a detailed explanation of the resistance caused by triple mutant (V32I, I47V and V82I) and may give imperative clue for the design of drugs to combat amprenavir resistance.
Published Version
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