Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro

The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and thus is a target for drug discovery teams. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors.

Here, we report the development of specific, noncovalent inhibitors of 3CLpro with high in vivo efficacy in mice.

One compound, WU-04, exhibited anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice.

https://pubmed.ncbi.nlm.nih.gov/36844503/

Publication_Development of highly potent non-covalent inhibitors of SARS-CoV-2 3CLpro

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