Molecular docking unmasks potent phytoligands against sars-cov-2 spike glycoprotein, main protease, papain-like protease, and RNA-dependent RNA polymerase

Abstract

The recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has offered a unique challenge for human survival. However, there is no available known prophylaxis, therapeutic intervention, and vaccine candidate against SARS-CoV-2 to date. We aimed towards identifying novel phytoligands from widely available botanical resources which could serve as potential inhibitors against SARS-CoV-2. Based on literature review, database search, ADMET, and drug-likeness, 55 phytoligands and 8 synthetic repurposing drugs were screened and tested against SARS-CoV-2 spike glycoprotein, main protease, papain-like protease, and RNA-dependent RNA polymerase using molecular docking and protein-ligand interaction. All phytoligands and repurposing drugs showed binding affinity based inhibitory potential against the viral proteins. The highest binding affinities of phytoligands towards antiviral targets were exhibited by colchicine and oleic acid, and that of repurposing drugs was shown by saquinavir and nelfinavir. Capsaicin, oleic acid, azithromycin, nelfinavir, remdesivir, and saquinavir were acted as plausible broad-spectrum inhibitors. Hydrogen bonds and hydrophobic interactions of amino acids were varied significantly within the conserved domain along with glutamic acid richness. Further investigation should be carried out to obtain the synergistic effect using cell-based assays, animal models, and clinical trials to discover novel phytomedicine against SARS-CoV-2.