Understanding Viral Main Protease as a Target for a Potential COVID-19 Treatment

A primer breaking down “Discovery of M Protease Inhibitors Encoded by SARS-CoV-2”

  • Quinn Heutmaker University of Minnesota-Duluth


Background: As of the publication of this primer, the SARS-CoV-2 pandemic continues, along with the search for a treatment. Given the urgency of the research, previously tested treatments and compounds are being repurposed with hopes that they will be effective against the virus. Hung et al. (2020) decided to investigate one of these compounds as part of the treatment search. This primer will explore their investigation. Results: Hung and colleagues investigated the protease inhibitor GC376 as a potential treatment for SARS-CoV-2. GC376 inhibits the viral main protease (Mpro) of SARSCoV-2, a key protein in viral replication. It was selected as GC376 previously demonstrated effectiveness against another coronavirus, Feline Infectious Peritonitis Virus (FIPV), which has a similar Mpro structure. They observed a stronger binding affinity of GC376 to SARS-CoV-2 Mpro than FIPV Mpro. Additionally, they found an effective dose of GC376 was significantly smaller than the dose needed to induce toxic effects. Conclusion: Since the publication of Hung et al.’s (2020) article, other researchers have published work on GC376 in the search for a SARS-CoV-2 treatment. Overall, Hung et al.’s (2020) results have been supported, and it has been agreed that GC376 should be further investigated as a potential treatment.