X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease.
Science
; 372(6542): 642-646, 2021 05 07.
Article
in English
| MEDLINE | ID: covidwho-1166347
ABSTRACT
The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput x-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast to commonly applied x-ray fragment screening experiments with molecules of low complexity, our screen tested already-approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to Mpro In subsequent cell-based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Protease Inhibitors
/
Catalytic Domain
/
Allosteric Site
/
Drug Development
/
Coronavirus 3C Proteases
/
SARS-CoV-2
Type of study:
Prognostic study
Topics:
Traditional medicine
Limits:
Animals
Language:
English
Journal:
Science
Year:
2021
Document Type:
Article
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