Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening

International Journal of Biological Macromolecules
Olga AbianAdrian Velazquez-Campoy

Abstract

The global health emergency generated by coronavirus disease 2019 (COVID-19) has prompted the search for preventive and therapeutic treatments for its pathogen, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are many potential targets for drug discovery and development to tackle this disease. One of these targets is the main protease, Mpro or 3CLpro, which is highly conserved among coronaviruses. 3CLpro is an essential player in the viral replication cycle, processing the large viral polyproteins and rendering the individual proteins functional. We report a biophysical characterization of the structural stability and the catalytic activity of 3CLpro from SARS-CoV-2, from which a suitable experimental in vitro molecular screening procedure has been designed. By screening of a small chemical library consisting of about 150 compounds, the natural product quercetin was identified as reasonably potent inhibitor of SARS-CoV-2 3CLpro (Ki ~ 7 μM). Quercetin could be shown to interact with 3CLpro using biophysical techniques and bind to the active site in molecular simulations. Quercetin, with well-known pharmacokinetic and ADMET properties, can be considered as a good candidate for further optimization and deve...Continue Reading

Associated Clinical Trials

Citations

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Methods Mentioned

BETA
differential scanning calorimetry
FRET
thermal shift
PCR
isothermal titration calorimetry
circular dichroism
Fluorescence
gel filtration
Isothermal
dynamic light scattering

Software Mentioned

AutoDock Vina
OriginLab
Origin
AutoDock Tools
Avogadro

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