Background: Tremendous research from last twenty years has been pursued to cure human life against HIV virus. A\r\nlarge number of HIV protease inhibitors are in clinical trials but still it is an interesting target for researchers due to\r\nthe viral ability to get mutated. Mutated viral strains led the drug ineffective but still used to increase the life span\r\nof HIV patients.\r\nResults: In the present work, 3D-QSAR and docking studies were performed on a series of Danuravir derivatives,\r\nthe most potent HIV- protease inhibitor known so far. Combined study of 3D-QSAR was applied for Danuravir\r\nderivatives using ligand-based and receptor-based protocols and generated models were compared. The results\r\nwere in good agreement with the experimental results. Additionally, docking analysis of most active 32 and least\r\nactive 46 compounds into wild type and mutated protein structures further verified our results. The 3D-QSAR and\r\ndocking results revealed that compound 32 bind efficiently to the wild and mutated protein whereas, sufficient\r\ninteractions were lost in compound 46.\r\nConclusion: The combination of two computational techniques would helped to make a clear decision that\r\ncompound 32 with well inhibitory activity bind more efficiently within the binding pocket even in case of mutant\r\nvirus whereas compound 46 lost its interactions on mutation and marked as least active compound of the series.\r\nThis is all due to the presence or absence of substituents on core structure, evaluated by 3D-QSAR studies. This set\r\nof information could be used to design highly potent drug candidates for both wild and mutated form of viruses.
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