Authors: Harriet Wall, Future Science Group
In a collaborative study between the University of South Florida (USF Health; FL, USA) and the University of Arizona College of Pharmacy (AZ, USA), several existing drugs have been identified as potential therapies for COVID-19. The study has been published in the Nature journal, Cell Research.
Drug repurposing, similar to recycling, is a method used to identify old drugs for new therapeutic purposes. During the COVID-19 pandemic, drug repurposing has gained a lot of attention.
“With a rapidly emerging infectious disease like COVID-19, we don’t have time to develop new antiviral drugs from scratch,” explained Yu Chen (USF Health) associate professor of molecular medicine. “A lot of good drug candidates are already out there as a starting point. But, with new information from studies like ours and current technology, we can help design even better (repurposed) drugs much faster.”
Their study utilized advanced techniques such as X-ray crystallography and molecular docking to successfully identify four potential drugs; Boceprevir, GC-376 and Calpain inhibitors II and XII. These were initially investigated for use in Hepatitis C, coronavirus in cats, and cancer, respectively.
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All four drugs target the SARS-CoV-2 main protease (Mpro), an enzyme that is essential for the replication and survival of the virus.
Promisingly, Mpro isn’t expressed in human cells – meaning that targeting this enzyme should only affect the virus, and is less likely to cause side effects.
The efficacy of the potential repurposed drugs can be measured by how well the molecule binds to the enzyme, much like a key fitting into a lock.
“GC-376 was by far the key with the best, or tightest, fit,” commented Chen. “Our modeling shows how the inhibitor can mimic the original peptide substrate when it binds to the active site on the surface of the SARS-CoV-2 main protease.”
Sources: Ma C, Sacco MC, Hurst B, et al. Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Res. doi:10.1038/s41422-020-0356-z (2020); https://hscweb3.hsc.usf.edu/blog/2020/07/06/compounds-halt-sars-cov-2-replication-by-targeting-key-viral-enzyme/