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Title: Molecular characterization of ebselen binding activity to SARS-CoV-2 main protease
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, M pro , 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 M pro 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.  more » « less
Award ID(s):
1828629
PAR ID:
10198998
Author(s) / Creator(s):
; ; ; ;
Date Published:
Journal Name:
Science Advances
Volume:
6
Issue:
37
ISSN:
2375-2548
Page Range / eLocation ID:
eabd0345
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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