Inhibitory Activity of Flavonoid Scaffolds on SARS-CoV-2 3CLpro: Insights from the Computational and Experimental Investigations

• DOI: 10.1021/acs.jcim.3c01477
• Publication Date: 2024-01-26T16:04:53Z
• Authors: Nopawit Khamto; Kraikrit Utama; Panida Boontawee; Atchara Janthong; Suriya Tatieng; Supakorn Arthan; Vachira Choommongkol; Padchanee Sangthong; Chavi Yenjai; Nuttee Suree; Puttinan Meepowpan
• Keywords: Vero cell; Baicalein

The emergence of the COVID-19 situation has become a global issue due to lack effective antiviral drugs for treatment. Flavonoids are class plant secondary metabolites that have activity against SARS-CoV-2 through inhibition main protease (3CLpro). In this study, 22 flavonoids obtained from natural sources and semisynthetic approaches were investigated their inhibitory 3CLpro, along with cytotoxicity on Vero cells. protein–ligand interactions examined using molecular dynamics simulation. Moreover, QSAR analysis was conducted clarify structural effects bioactivity. Accordingly, in vitro investigation demonstrated four flavonoids, namely, tectochrysin (7), 6″,6″-dimethylchromeno-[2″,3″:7,8]-flavone (9), panduratin A (19), genistein (20), showed higher compared standard flavonoid baicalein. Finally, our finding suggests an isoflavone discovered Millettia brandisiana, potential further development as 3CLpro inhibitor.