Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro.
ACS Cent Sci
; 9(2): 217-227, 2023 Feb 22.
Article
in English
| MEDLINE | ID: covidwho-2241536
ABSTRACT
The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, noncovalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC50 values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment.
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Collection:
International databases
Database:
MEDLINE
Language:
English
Journal:
ACS Cent Sci
Year:
2023
Document Type:
Article
Affiliation country:
Acscentsci.2c01359
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