Inhibitory Activity of Flavonoid Scaffolds on SARS-CoV-2 3CL pro : Insights from the Computational and Experimental Investigations.
Nopawit KhamtoKraikrit UtamaPanida BoontaweeAtchara JanthongSuriya TatiengSupakorn ArthanVachira ChoommongkolPadchanee SangthongChavi YenjaiNuttee SureePuttinan MeepowpanPublished in: Journal of chemical information and modeling (2024)
The emergence of the COVID-19 situation has become a global issue due to the lack of effective antiviral drugs for treatment. Flavonoids are a class of plant secondary metabolites that have antiviral activity against SARS-CoV-2 through inhibition of the main protease (3CL pro ). In this study, 22 flavonoids obtained from natural sources and semisynthetic approaches were investigated for their inhibitory activity against SARS-CoV-2 3CL pro , along with cytotoxicity on Vero cells. The protein-ligand interactions were examined using molecular dynamics simulation. Moreover, QSAR analysis was conducted to clarify the structural effects on bioactivity. Accordingly, the in vitro investigation demonstrated that four flavonoids, namely, tectochrysin ( 7 ), 6″,6″-dimethylchromeno-[2″,3″:7,8]-flavone ( 9 ), panduratin A ( 19 ), and genistein ( 20 ), showed higher protease inhibitory activity compared to the standard flavonoid baicalein. Finally, our finding suggests that genistein ( 20 ), an isoflavone discovered in Millettia brandisiana , has potential for further development as a SARS-CoV-2 3CL pro inhibitor.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- molecular dynamics simulations
- anti inflammatory
- molecular docking
- induced apoptosis
- ms ms
- cell cycle arrest
- small molecule
- amino acid
- mass spectrometry
- molecular dynamics
- cell death
- combination therapy
- high resolution
- replacement therapy
- single molecule
- drug induced
- tissue engineering
- pi k akt
- high speed