Abstract

Background: The newly emerged delta and omicron variants of severe acute respiratory syndrome coronavirus (SARS-CoV-2) have affected millions of individuals globally with increased transmissible and infectivity rates. Although, numerous vaccines are available or under clinical trials to combat the SARS-CoV-2 and its variant, still, a therapeutic agent is awaited.

Objective: The present work is focused on rigorous screening of chemical constituents of Azadirachta indica (A. indica) against delta and omicron variants of SARS-CoV-2 via inhibition of S-glycoprotein.

Methods: Total, 10 compounds of A. indica were subjected to molecular docking and pharmacophore modeling studies against the S-glycoprotein of delta and omicron variants of SARS-CoV-2. Furthermore, homology modeling was performed for omicron S-glycoprotein with the help of SWISS-MODEL and aligned by PyMOL software. Later on, the residues of protein were verified in the allowed region via Ramachandran plot. In addition, our docking results have also been validated by MMGBSA binding free energy calculations.

Results: Our computed study demonstrated that nimbolinin B12-methyl ether and nimbidinin showed promising docking scores (> -6.0) as compared to docking scores (< 6.0) of reference drug ‘camostat’ against S-glycoproteins of both delta and omicron variants. Redocking by using MMGBSA calculation also reveals that both these compounds can effectively bind within the pockets of said protein receptors.

Conclusion: Nimbolinin B12-methyl ether and nimbidinin have potent anti-SARS-CoV activity against delta and omicron variants and thus, A. indica might be a useful source for developing novel anti-SARSCoV- 2 therapeutic agents.

Keywords: Azadirachta indica, nimbolinin B12-methyl ether, nimbidinin, homology modeling, molecular docking, MMGBSA calculation, ramachandran plot.

Graphical Abstract