Comprehensive in silico screening of flavonoids against SARS-CoV-2 main protease.

ABSTRACT

In the current pandemic caused by the new coronavirus (SARS-CoV-2), computational drug discovery can play an essential role in finding potential therapeutic agents. Thanks to its anti-viral, antibacterial, and anti-inflammatory properties, sage (Salvia officinalis) is used in traditional medicine. In this study, drugs proposed against COVID-19, including Lopinavir, Remdesivir, Favipiravir, and main flavonoids of sage, were docked favorably against novel coronavirus main protease. Molecular docking findings indicate that Rutin, Luteolin-7-glucoside, Apigenin, and Hispidulin make strong interactions with better binding affinity than selected commercial drugs in the study. But Rutin is the only flavonoid that makes strong hydrogen bond interactions with catalytic dyad and crucial Mpro residues and has more binding affinity than protease inhibitor PF-07321332 as an oral antiviral (PAXLOVID™). Further analysis of Molecular Dynamics and MM-PBSA predicted that chosen ligands could form stable complexes with the main protease. Also, ADMET analysis shows that main flavonoids are expected to have appropriate pharmacokinetic and no toxic properties. The results of the in silico study suggest that Salvia officinalis as a rich source of potent anti-coronavirus flavonoids may play a significant role in counteracting the replication of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.