In-Silico Study of Resveratrol as Multi-Edged Potent Inhibitor against SARS-Cov-2 and Variants of Concern Using Molecular Dynamic Simulation and PCA Analysis



Novel Coronavirus infection was announced as a global pandemic by the World Health Organization owing to its high spread and pathogenicity. In due course, there are a few approved drug molecules available for the treatment of SARS-CoV-2 infections, and a few more drugs are in the pipeline of clinical trials. However, a recent challenge has come up with rapid mutations on several proteins including the S protein of SARS-CoV-2. Multi-targeted (polypharmacological) therapy may be an effective strategy for the treatment of SARS-CoV-2 and its emerging variants.



In this study, we performed structure and pharmacophore-based screening by considering more than 12,000 compounds from FDA-approved drugs, antiviral drugs, anticancer drugs, and bioactive molecules from spices, vegetables, and fruits against the main protease (Mpro) enzyme of SARS-CoV-2.



Virtual screening was performed by molecular docking. Furthermore, the best-selected molecule resveratrol was rescreened and subjected to docking, MMGBSA, molecular dynamic simulation, and principle component analysis (PCA) with 09 more essential (normal) target proteins and 02 spike variants (Delta / Omicron spike protein in complex with human ACE2) of SARS-CoV-2 to investigate multi-targeting potency of resveratrol.



Thus, all in-silico studies and their analyses show, resveratrol might serve as a potential multi-targeting molecule. Molecular dynamics simulation of 100 ns substantiated the strong interactions of proteins with resveratrol. The proposed molecule has strong interactions with 07 normal and mutated spike (S-RBD-ACE2) proteins of SARS-CoV-2.



The present study demonstrated that resveratrol may be useful for polypharmacological therapy against normal/mutated variants of SARS-CoV-2 to address the ongoing pandemic.
