Structure-based virtual screening, ADMET profiling, and molecular dynamics simulation studies on HIV-1 protease for identification of active phytocompounds as potential anti-HIV agents

Abstract

ABSTRACT HIV-1 protease (HIV-pr) acts as the most promising drug target commonly used for anti-HIV therapy. However, the efficiency of the protease inhibitors (PIs) has been greatly reduced by mutations assisted drug resistance. Because of the richness and greatest diversity of plants, the current study aims at exploring phytocompounds as PIs with potential inhibitory properties against HIV-pr through multi-faceted in silico tactics. Virtually screened phytocompounds (Epicatechin, Epigallocatechol, D-Catechin, Afrormosin and Afzelechin) were employed via docking to the WT and I50V mutant. Molecular dynamics of complexed HIV-pr with 50 ns trajectory expose that the nominated phytocompounds can efficiently bind to the HIV-pr active site and control the flap dynamics. The relative binding free energies for the five phytocompounds to both WT and I50V mutant were calculated by MM-GBSA method. The increased binding affinity was witnessed for most of the PIs (except AFZ), and on account of the robust binding, which may be primarily accredited due to the upsurge in ΔE ele and ΔE vdw, the I50V mutant might be well acclimatised by the PIs. Overall, this study led to the identification of potential hit compounds like Epigallocatechol with favourable pharmacokinetic properties for both WT and I50 V may lead to the discovery of robust new drugs against HIV-pr.