Identification of ZINC inhibitors for HIV-1 Protease through Structure-Based Pharmacophore, Virtual Screening, ADMET and Molecular Dynamics Simulation

Treating HIV is made difficult by the evolution of antimicrobial resistant mutants that occurs in life cycle this virus. This has led to numerous inhibition mechanism intends challenges replication One such approach application molecular modelling drug discovery. In study computer aided design were employed finding an inhibitor can contribute a suitable candidate. Firstly, ZINC database was screened using Lipinski’s rule five, and compounds having similar biological features classified grouped together into compound library. Secondly, co-crystallized structure 1rv7 wild type HIV-1 protease used construct pharmacophore model screen further, Ligand stored Thestructure-basedpharmacophore created mimicking three main active from Protein Data Bank, namely, 82 84, I50 I150 residues.Thirdly, total twenty-six had less than 0,5 RMSD identified selected. Fourthly, based on best docking ligands, ten these high binding affinity These are ZINC_001456687980 (-8.0), ZINC_001445792073 (-7.8) ZINC_001461099137 (-7.4), successively. However, eliminated unfavorable donor-donor interaction. The subsequent compound, ZINC_000015276352 then placed top leading with (-6.9). Fifthly, ADMET property analysis compounds, satisfied were, ZINC_001456687980, ZINC_000015276352, ZINC_001359888321 ZINC_001460445290. properties included BBB permeation, gastrointestinal absorption, pan assay interference (PAINS), analyzed. two violation (mw >350, XLOGP3>3.5),whiles violations > 350, XLOGP3 3.5, rotatable 7). Lastly, only underwent dynamics simulations. Molecular simulation revealed formation bond interactions between target protein.