Molecular Dynamics and Free Energy Landscape Study of SARS‐CoV‐2 Omicron Mpro Boswellic acid Compounds of Boswellia Serrata Inhibitors

Abstract

AbstractThis work sheds light on the effect of boswellic acid compounds (Alpha boswellic acid, Beta boswellic acid, 11‐keto beta boswellic acid and 3‐Acetyl‐11‐keto beta boswellic acid) upon inhibiting SARS‐CoV‐2 Mpro and O‐Mpro (Main protease). A good docking score (−8.4 kcal/mol) is found in the case of 3‐Acetyl‐11‐keto beta boswellic acid as compared to the reference and three other boswellic acid compounds. ADMET results suggest that all these compounds are nontoxic and their pharmacokinetic properties are satisfactory. Moreover, a stability analysis with Mpro/O‐Mpro through RMSD, RMSF, hydrogen bonds and Rg parameters in MD simulations is made and we found better values than the reference case. Pre and post‐MD structures of Ligands‐Mpro show a similar binding site whereas a drift can be noted for L‐O‐Mpro. 3‐Acetyl‐11‐keto beta boswellic acid shows an average of five hydrogen bonds and it remains stable within the binding pocket of Mpro during the simulation period in comparison to other boswellic acids compounds. Various metastable conformations are observed for all compounds in FEL (free energy landscape), however, Acyclovir‐Mpro, Alpha boswellic acid‐Mpro and Beta boswellic acid‐O‐Mpro display only one global minimum. The results suggest that these compounds can be used as potential lead molecules for breakthroughs in drug discovery.