Natural compounds as potential inhibitors of SARS-CoV-2 main protease
Amaresh Mishra, Yamini Pathak, Anuj Kumar, Surabhi Kirti Mishra, Vishwas Tripathi · Asian Pacific Journal of Tropical Biomedicine · 2021
Objective: To explore natural compounds as potential inhibitors against main protease (M pro ) of SARS-CoV-2. Methods: In the current study, systematic molecular docking analysis was conducted using AutoDock 4.2 to determine the binding affinities and interactions between natural compounds and M pro . Selected natural compounds were further validated using a combination of molecular dynamic (MD) simulations and molecular mechanic Poisson-Boltzmann surface area (MM/PBSA) free energy calculations. Results: Out of twenty natural compounds, four natural metabolites namely, amentoflavone, guggulsterone, puerarin, and piperine were found to have strong interaction with M pro of SARS-CoV-2 based on docking analysis. During MD simulations, all four natural compounds bound to M pro at 50 ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands had stable and favorable energies with strong binding to M pro protein. Conclusions: Guggulsterone is a potential inhibitor of COVID- 19 main protease M pro . Further in vitro and pre-clinical studies are needed.