Objective:To explore natural compounds as potential inhibitors against main protease(Mpro)of SARS-CoV-2.Methods:In the current study,systematic molecular docking analysis was conducted using AutoDock 4.2 to determine ...Objective:To explore natural compounds as potential inhibitors against main protease(Mpro)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 Mpro.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 c alculation s.Results:Out of twenty natural compounds,four natural metabolites namely,amentoflavone,guggulsterone,puerarin,and piperine were found to have strong interaction with Mpro of SARS-CoV-2 based on docking analysis.During MD simulations,all four natural compounds bound to Mpro 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 Mpro protein.Conclusions:Guggulsterone is a potential inhibitor of COVID-19 main protease Mpro.Further in vitro and pre-clinical studies are needed.展开更多
文摘Objective:To explore natural compounds as potential inhibitors against main protease(Mpro)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 Mpro.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 c alculation s.Results:Out of twenty natural compounds,four natural metabolites namely,amentoflavone,guggulsterone,puerarin,and piperine were found to have strong interaction with Mpro of SARS-CoV-2 based on docking analysis.During MD simulations,all four natural compounds bound to Mpro 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 Mpro protein.Conclusions:Guggulsterone is a potential inhibitor of COVID-19 main protease Mpro.Further in vitro and pre-clinical studies are needed.
