Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32855413.
- Also identified by DOI 10.1038/s41467-020-18096-2 and PMC identifier 7453019.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The main protease, M<sup>pro</sup> (or 3CL<sup>pro</sup>) in SARS-CoV-2 is a viable drug target because of its essential role in the cleavage of the virus polypeptide. Feline infectious peritonitis, a fatal coronavirus infection in cats, was successfully treated previously with a prodrug GC376, a dipeptide-based protease inhibitor. Here, we show the prodrug and its parent GC373, are effective inhibitors of the M<sup>pro</sup> from both SARS-CoV and SARS-CoV-2 with IC<sub>50</sub> values in the nanomolar range. Crystal structures of SARS-CoV-2 M<sup>pro</sup> with these inhibitors have a covalent modification of the nucleophilic Cys145. NMR analysis reveals that inhibition proceeds via reversible formation of a hemithioacetal. GC373 and GC376 are potent inhibitors of SARS-CoV-2 replication in cell culture. They are strong drug candidates for the treatment of human coronavirus infections because they have already been successful in animals. The work here lays the framework for their use in human trials for the treatment of COVID-19.
Medical subject headings
- Antiviral Agents
- Betacoronavirus
- Coronavirus, Feline
- Protease Inhibitors
- Viral Nonstructural Proteins