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

SARS‐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.

A Theoretical Study To Understand the Impact of Mpro of nCoV on the Hormones

“…A reference set of positions was used to calculate the standard deviation of atoms from their respective mean position. RMSF is a numeric measurement that is similar to RMSD, however rather than showing how the positions of whole structures change over time, RMSF calculates how flexible each residue is, or how much it moves (varies) during a simulation [44–47] . Lesser the fluctuation, stable the complex.…”

“…RMSF is a numeric measurement that is similar to RMSD, however rather than showing how the positions of whole structures change over time, RMSF calculates how flexible each residue is, or how much it moves (varies) during a simulation. [44][45][46][47] Lesser the fluctuation, stable the complex. Also, the development of a ligand-protein complex relies heavily on non-covalent interactions like hydrogen bonding.…”

Harnessing Brazilian biodiversity database: identification of flavonoids as potential inhibitors of SARS-CoV-2 main protease using computational approaches and all-atom molecular dynamics simulation

“…Although COVID-19 vaccines have been developed remarkably quickly, it remains uncertain how well they will perform in the long term and whether they will be effective against potential future variants of SARS-CoV-2 and other coronaviruses ( Heaton, 2020 ; Jackson et al, 2020 ; Yu et al, 2020 ; Panda et al, 2023 ). With commercially available antiviral treatments proving to be extremely ineffective ( Liu et al, 2022 ; Purohit et al, 2023 ), the need for the search for potentially more effective antivirals arises.…”

“…Due to the urgent need to find an effective therapy to combat SARS-CoV-2, several studies have emphasized the importance of Natural Products (NPs) as potential antiviral agents ( Antonio et al, 2020 ; Islam et al, 2020 ; Mani et al, 2020 ; Wang and Yang, 2020 ; Rubio-Martínez et al, 2021 ). Furthermore, some research has focused on the use of NPs as inhibitors of the main protease of SARS-CoV-2 (Mpro) ( Aanouz et al, 2021 ; Ray et al, 2022 ; Ahamed and Arif, 2023 ; Purohit et al, 2023 ).…”