Phytocompounds as versatile drug-leads targeting mProtease in the SARS-CoV-2 virus: insights from a molecular dynamics study

SARS-CoV-2 is one of the deadly outbreaks in the present era and still showing its presence around the globe. Researchers have produced various vaccines that offer protection against infection, but we have not yet found a cure for COVID-19. Currently, efforts are focused on identifying effective therapeutic approaches to treat this infectious disease. In the present work, we investigated the main protease (Mpro) protein, a crucial component in SARS-CoV-2 viral particle formation, as a drug target and proposed phytocompounds with therapeutic potential against SARS-CoV-2. Initially, several plant-based resources were exploited to screen around one thousand phytocompounds and further their physiochemical characterization and assessment of drug likeliness were performed using SwissADME. Eventually, we screened 95 compounds based on docking analysis using AutoDock Vina. Five compounds were selected having the highest affinity for Mpro for the analysis of ligand-receptor interaction using molecular dynamic (MD) simulation. Docking and MD simulation studies elucidated the promising stable interaction of selected 5 ligands with Mpro. During MD simulation of 100 ns, Abacopterin F showed the lowest binding energy (–37.13 kcal/mol) with the highest affinity towards Mpro and this compound may be proposed as a lead molecule for further investigation. This interaction may result in modulation of the Mpro activity, consequently leading to hindrance in viral particle formation. However, in-vitro and in-vivo experimental validation would be needed to process the selected phytomolecules as a therapeutic lead against SARS-CoV-2.