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A new weapon against SARS-CoV-2

Created by Timothy Paustian on Jul 26, 2020, 10:29 PM

 

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Holy COVID inhibition Batman. Hung et. al may have found a powerful weapon against SARS-CoV-2. A study of a known candidate drug (GC376) used to treat feline infectious peritonitis virus, is showing potent inhibition of SARS-CoV-2. The drug is an M protease inhibitor. These proteases are common in RNA viruses. The virus genome mimics an mRNA and is translated at the host ribosome. The problem is, eukaryotic ribosomes only make one protein from one mRNA, but the virus has a number of proteins that need to be translated. SARS-CoV-2's solution (as is true for many RNA viruses) is to encode a giant polyprotein and a protease that chops up the polyprotein after translation. This way all the various virus proteins are released and can do their function. The protein that does this function for SARS-CoV-2 is the M protein. It is a great target for drugs because humans don't make polyprotein proteases.

GC376 has potent activity against the M protein, inhibiting it at nanomolar concentrations (That is one-billionth of a gram per liter of water). In viral replication assays using human Vero cells, it had a half-maximum effective concentration (IC50) of 0.91 µM. In comparison, remdesivir has an IC50 of 11.41. That is about one part per billion, so it is working at very small concentrations. The drug is under investigation to treat feline infectious peritonitis virus in cats, where it has been demonstrated to cure this fatal disease. It is well tolerated in cats, where the drug was well tolerated at a dose of 10 mg/kg/dose, which was enough to raise the concentrations of the drug in plasma to 2 µM, well above it's potential effective concentration. This drug should be rapidly investigated for the treatment of SARS-CoV-2.