Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32887884.
- Also identified by DOI 10.1038/s41467-020-18233-x and PMC identifier 7474075.
- 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
COVID-19 was declared a pandemic on March 11 by WHO, due to its great threat to global public health. The coronavirus main protease (M<sup>pro</sup>, also called 3CLpro) is essential for processing and maturation of the viral polyprotein, therefore recognized as an attractive drug target. Here we show that a clinically approved anti-HCV drug, Boceprevir, and a pre-clinical inhibitor against feline infectious peritonitis (corona) virus (FIPV), GC376, both efficaciously inhibit SARS-CoV-2 in Vero cells by targeting M<sup>pro</sup>. Moreover, combined application of GC376 with Remdesivir, a nucleotide analogue that inhibits viral RNA dependent RNA polymerase (RdRp), results in sterilizing additive effect. Further structural analysis reveals binding of both inhibitors to the catalytically active side of SARS-CoV-2 protease M<sup>pro</sup> as main mechanism of inhibition. Our findings may provide critical information for the optimization and design of more potent inhibitors against the emerging SARS-CoV-2 virus.
Medical subject headings
- Betacoronavirus
- Coronavirus Infections
- Pneumonia, Viral
- Proline
- Protease Inhibitors
- Pyrrolidines
- Viral Nonstructural Proteins