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 (Mpro, 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 Mpro. 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 Mpro 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.
Highlights
COVID-19 was declared a pandemic on March 11 by World Health Organization (WHO), due to its great threat to global public health
We found that the Mpro of SARS-CoV-2 has high homology with other CoV Mpro (Supplementary Fig. 1)
Boceprevir and GC376, can inhibit the enzymatic activity well (Fig. 1b)
Summary
COVID-19 was declared a pandemic on March 11 by WHO, due to its great threat to global public health. Recent studies have shown that the SARS-CoV-2 uses the same Angiotensin-converting enzyme 2 (ACE2) receptor as SARS-CoV4, and the structural basis of receptor recognition was quickly elucidated to provide important basis for the molecular understanding of virus entry process and the development of potential antiviral inhibitors[15,16,17,18] Some old drugs such as Remdesivir, Favipiravir, and Chloroquine/Hydroxychloroquine, and traditional Chinese medicines showed potential for the treatment of COVID-1919–22. As there is neither specific antiviral agents nor available vaccines, repurposing of clinically approved drugs to combat the COVID-19 is urgently needed We show both Boceprevir and GC376 can inhibit Mpro activity and SARS-CoV-2 in Vero cells. These data provide critical information for the optimization and design of more potent inhibitors against the emerging pathogen SARS-CoV-2
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