tetano
Editor, Senior Moderator
Biochem Biophys Res Commun
. 2022 Mar 10;604:76-82.
doi: 10.1016/j.bbrc.2022.03.052. Online ahead of print.
Discovery of 4'-O-methylscutellarein as a potent SARS-CoV-2 main protease inhibitor
Qianqian Wu[SUP] 1 [/SUP], Shiqiang Yan[SUP] 2 [/SUP], Yujie Wang[SUP] 2 [/SUP], Maotian Li[SUP] 3 [/SUP], Yibei Xiao[SUP] 4 [/SUP], Yingxia Li[SUP] 5 [/SUP]
Affiliations
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and seriously threatened public health and safety. Despite COVID-19 vaccines being readily popularized worldwide, targeted therapeutic agents for the treatment of this disease remain very limited. Here, we studied the inhibitory activity of the scutellarein and its methylated derivatives against SARS-CoV-2 main protease (M[SUP]pro[/SUP]) by the fluorescence resonance energy transfer (FRET) assay. Among all the methylated derivatives we studied, 4'-O-methylscutellarein exhibited the most promising enzyme inhibitory activity in vitro, with the half-maximal inhibitory concentration value (IC[SUB]50[/SUB]) of 0.40 ± 0.03 μM. Additionally, the mechanism of action of the hits was further characterized through enzyme kinetic studies and molecular docking. Overall, our results implied that 4'-O-methylscutellarein could be a primary lead compound with clinical potential for the development of inhibitors against the SARS-CoV-2 M[SUP]pro[/SUP].
Keywords: COVID-19; M(pro) inhibitor; SARS-CoV-2; Scutellarein.
. 2022 Mar 10;604:76-82.
doi: 10.1016/j.bbrc.2022.03.052. Online ahead of print.
Discovery of 4'-O-methylscutellarein as a potent SARS-CoV-2 main protease inhibitor
Qianqian Wu[SUP] 1 [/SUP], Shiqiang Yan[SUP] 2 [/SUP], Yujie Wang[SUP] 2 [/SUP], Maotian Li[SUP] 3 [/SUP], Yibei Xiao[SUP] 4 [/SUP], Yingxia Li[SUP] 5 [/SUP]
Affiliations
- PMID: 35303682
- PMCID: PMC8907111
- DOI: 10.1016/j.bbrc.2022.03.052
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and seriously threatened public health and safety. Despite COVID-19 vaccines being readily popularized worldwide, targeted therapeutic agents for the treatment of this disease remain very limited. Here, we studied the inhibitory activity of the scutellarein and its methylated derivatives against SARS-CoV-2 main protease (M[SUP]pro[/SUP]) by the fluorescence resonance energy transfer (FRET) assay. Among all the methylated derivatives we studied, 4'-O-methylscutellarein exhibited the most promising enzyme inhibitory activity in vitro, with the half-maximal inhibitory concentration value (IC[SUB]50[/SUB]) of 0.40 ± 0.03 μM. Additionally, the mechanism of action of the hits was further characterized through enzyme kinetic studies and molecular docking. Overall, our results implied that 4'-O-methylscutellarein could be a primary lead compound with clinical potential for the development of inhibitors against the SARS-CoV-2 M[SUP]pro[/SUP].
Keywords: COVID-19; M(pro) inhibitor; SARS-CoV-2; Scutellarein.