In June of 2020, researchers from University of Arizona, University of South Florida Morsani College of Medicine, and Utah State University published an article through Nature titled “Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease”. Their goal was aligned with that of many of today’s researchers: find a way to fight Covid-19 (SARS-CoV-2). In this study, the researchers explored a potential target for antiviral drug therapy by targeting the SARS-CoV-2 main protease (Mpro). Mpro plays a vital role in SARS-CoV-2 replication, and therefore presents an excellent target for potential antiviral therapy.
In the first round of this study, the researchers tested 55 different existing protease inhibitors to determine their efficacies against Mpro. There were four frontrunners, including the calpain inhibitor MG-132. This led to the second round of the study, which tested the efficacies of eight additional commercially available calpain and cathepsin inhibitors and two viral 3CL protease inhibitors. Following the second round, it was discovered that Boceprevir, GC-376, and three of the calpain/cathepsin inhibitors were strong inhibitors of Mpro.
The most potent inhibitors of Mpro were the calpain/cathepsin inhibitors, of which there are currently several commercially available. Commercial availability will speed up the process for FDA approval as an antiviral against Covid-19, as the dose, toxicity, formulation, and PK properties are already known. This study has created a rich source of future study and development, and brings us closer to finding a safe antiviral therapy against the current pandemic.

By Jordan Lyons, PharmD candidate 2021
For full article, visit https://www.nature.com/articles/s41422-020-0356-z.pdf, published online 6/15/2020

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