Evaluating the Antiviral Potential of Phytocompounds from Mesua ferrea against SARS‐CoV‐2 Main Protease: Structure‐Based Virtual Screening and Molecular Dynamics Simulation Investigations

Abstract

AbstractSARS‐CoV‐2 is responsible for the novel coronavirus disease (COVID‐19) pandemic and poses a significant ongoing global risk due to increasing infection rates. Mesua ferrea Linn. (Ceylon Ironwood) is a rich source of botanical compounds with numerous medicinal properties, including antioxidant, antibacterial, antiviral, antitumor, and immunomodulatory properties seen commonly in Asian countries. Ten compounds of Mesua ferrea Linn i. e. Mesuferrol‐A, Mesuferrol‐B, Mesuaferrone‐A, Mesuaferrone‐B, Mesuol, Mammaesin, Mesuanic‐Acid, Euxanthone, Mammeigin, Mesuagin were stipulated for virtual screening against SARS‐CoV‐2 MPro. All inhibitory compounds were percolated according to docking scores and toxicity assessments. Three compounds i. e. Mesuagin, Mesuol, Mesuaferrol‐A, were observed with the highest binding free energies causing finer interactions with the active site residues of SARS‐CoV‐2 MPro which carries both non‐toxic and non‐carcinogenic properties. Molecular dynamics simulations were performed for 100 ns and free energies were calculated for the SARS‐CoV‐2‐MPro complex using MM‐GBSA to determine the relative binding affinities of the preferred molecules showing a network of interactions. The MM‐GBSA‐based approximations reveal that Mesuaferrol‐A (ΔGBind=−40.29 kcal/mol), is more viable in contrast to Mesuol (ΔGBind=−39.96 kcal/mol) and mesuagin (ΔGBind=−33.51 kcal/mol). The current investigation shows some possible insights towards the development of notably advantageous and effective anti‐SARS‐CoV‐2 MPro inhibitors.