Evaluation of binding performance of bioactive compounds against main protease and mutant model spike receptor binding domain of SARS-CoV-2: Docking, ADMET properties and molecular dynamics simulation study

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Phytochemicals present in medicinal plants have a variety of biological activities that help to combat against diseases. As part of efforts to study the binding performance of different phytochemicals derived from different plants like Zingiber officinale, Citrus limon, Syzygiumaromaticum, Ocimum tenuiflorum and Curcumin. We have screened 424 molecules. The binding affinity as well as physicochemical properties of the thebaine, acacetin, indomethacin, crinamineacetate, (S)-1-Piperideine-6-carboxylate, levamisole, melatonin, nicotinicacid, curcumin, methotrimeprazine, omeprazole, and methaqualone phytocompounds were analyzed through computational study. From the molecular docking study we found that, LEU50, ASN72, PRO96, TYR154, GLY170, ALA193, ARG222, and MET274 residues of main protease play a crucial role in binding with ligands. The present study revealed a noticeable interaction of GLY446, SER477, GLY482, THR500 and LEU518 residues with mutant of spike receptor binding domain SARS-CoV-2 protein were observed. Finally, 100 ns molecular dynamics simulation were used to study their dynamic properties as well as conformational flexibility. Free energy landscape analysis was performed of the 6LU7- acacetin and 6Y2E-acacetin systems and spike RBD-acacetin system. From molecular docking study and molecular dynamics study revealed that, the compound acacetin shows promising inhibitor towards both main protease as well as mutant spike RBD of SARS-CoV-2 protein.