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.
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Acknowledgments
The authors express deep sense of gratitude to the management of Vellore Institute of Technology for all the support, assistance and constant encouragements to carry out this work. The authors also thank reviewers for their valuable comments and suggestion in the improvement of our manuscript.
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Ramanathan, K., Shanthi, V., Pratik, U. et al. Computational analysis of amprenavir resistance triple mutant (V32I, I47V and V82I) in HIV-1 protease. Netw Model Anal Health Inform Bioinforma 3, 48 (2014). https://doi.org/10.1007/s13721-014-0048-z
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DOI: https://doi.org/10.1007/s13721-014-0048-z