Molecular characterization of ebselen binding activity to SARS-CoV-2 main protease.
Sci Adv
; 6(37)2020 09.
Article
in English
| MEDLINE | ID: covidwho-760208
ABSTRACT
There is an urgent need to repurpose drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent computational-experimental screenings have identified several existing drugs that could serve as effective inhibitors of the virus' main protease, Mpro, which is involved in gene expression and replication. Among these, ebselen (2-phenyl-1,2-benzoselenazol-3-one) appears to be particularly promising. Here, we examine, at a molecular level, the potential of ebselen to decrease Mpro activity. We find that it exhibits a distinct affinity for the catalytic region. Our results reveal a higher-affinity, previously unknown binding site localized between the II and III domains of the protein. A detailed strain analysis indicates that, on such a site, ebselen exerts a pronounced allosteric effect that regulates catalytic site access through surface-loop interactions, thereby inducing a reconfiguration of water hotspots. Together, these findings highlight the promise of ebselen as a repurposed drug against SARS-CoV-2.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Pneumonia, Viral
/
Azoles
/
Cysteine Endopeptidases
/
Organoselenium Compounds
/
Viral Nonstructural Proteins
/
Coronavirus Infections
/
Betacoronavirus
Limits:
Humans
Language:
English
Year:
2020
Document Type:
Article
Affiliation country:
Sciadv.abd0345
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