Dual-Reporter System for Real-Time Monitoring of SARS-CoV-2 Main Protease Activity in Live Cells Enables Identification of an Allosteric Inhibition Path.
ACS Bio Med Chem Au
; 2(6): 627-641, 2022 Dec 21.
Article
in English
| MEDLINE | ID: covidwho-2185502
ABSTRACT
The SARS-CoV-2 pandemic is an ongoing threat to global health, and the continuing emergence of contagious variants highlights the urgent need for additional antiviral therapy to attenuate COVID-19 disease. The SARS-CoV-2 main protease (3CLpro) presents an attractive target for such therapy due to its high sequence conservation and key role in the viral life cycle. In this study, we designed a fluorescent-luminescent cell-based reporter for the detection and quantification of 3CLpro intracellular activity. Employing this platform, we examined the efficiency of known protease inhibitors against 3CLpro and further identified potent inhibitors through high-throughput chemical screening. Computational analysis confirmed a direct interaction of the lead compounds with the protease catalytic site and identified a prototype for efficient allosteric inhibition. These developments address a pressing need for a convenient sensor and specific targets for both virus detection and rapid discovery of potential inhibitors.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Diagnostic study
Topics:
Variants
Language:
English
Journal:
ACS Bio Med Chem Au
Year:
2022
Document Type:
Article
Affiliation country:
Acsbiomedchemau.2c00034
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