pmid: 31724441,   nlmid 101150203,  doi:10.1080/14756366.2019.1690480

Inhibition of SARS-CoV 3CL protease by flavonoids.


Jo, Seri Kim, Suwon Shin, Dong Hae Kim, Mi-Sun

Vol. 35, Issue 35, Dec.2020

Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem),  ISSN 1475-6374

Abstract

There were severe panics caused by Severe Acute Respiratory Syndrome (SARS) and Middle-East Respiratory Syndrome-Coronavirus. Therefore, researches targeting these viruses have been required. Coronaviruses (CoVs) have been rising targets of some flavonoids. The antiviral activity of some flavonoids against CoVs is presumed directly caused by inhibiting 3C-like protease (3CLpro). Here, we applied a flavonoid library to systematically probe inhibitory compounds against SARS-CoV 3CLpro. Herbacetin, rhoifolin and pectolinarin were found to efficiently block the enzymatic activity of SARS-CoV 3CLpro. The interaction of the three flavonoids was confirmed using a tryptophan-based fluorescence method, too. An induced-fit docking analysis indicated that S1, S2 and S3' sites are involved in binding with flavonoids. The comparison with previous studies showed that Triton X-100 played a critical role in objecting false positive or overestimated inhibitory activity of flavonoids. With the systematic analysis, the three flavonoids are suggested to be templates to design functionally improved inhibitors.


MESH Headings


Article Keywords

FRET | SARS-CoV | SARS-CoV 3CLpro | flavonoid | inhibitory compounds |


Chemical

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