ChemRxiv | 2021
Nature Potential for COVID-19: Targeting SARS-CoV-2 Mpro Inhibitor with Bioactive Compound
Abstract
Corona viruses were first identified in 1931 and SARS-CoV-2 is the most recent COVID-19 is a pandemic that put most of the world on lockdown and the search for therapeutic drugs is still on-going Therefore, this study uses in silico screening to identify natural bioactive compounds from fruits, herbaceous plants and marine invertebrates that are able to inhibit protease activity in SARS-CoV-2(PDB: 6LU7) We have used various screening strategies such as drug likeliness, antiviral activity value prediction, molecular docking, ADME (absorption, distribution, metabolism, and excretion), molecular dynamics (MD) simulation and MM/GBSA (molecular mechanics/generalized born and surface area continuum solvation) 17 compounds were shortlisted using Lipinski’s rule 5 compounds revealed significantly good predicted antiviral activity values and out of them only 2 compounds, Macrolactin A and Stachyflin, showed good binding energy values of -9 22 and -8 00 kcal/mol within the binding pocket, catalytic residues (HIS 41 and CYS 145) of Mpro These two compounds were further analyzed for their ADME properties The ADME evaluation of these 2 compounds suggested that they could be effective as therapeutic agents for developing drugs for clinical trials MD simulations showed that protein-ligand complexes of Macrolactin A and Stachyflin were stable for 100 nano seconds The MM/GBSA calculations of Mpro – Macrolactin A complex indicated higher binding free energy (-42 58 ± 6 35 kcal/mol) with Mpro protein target receptor (6LU7) DCCM and PCA analysis on the residual movement in the