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Effect of COVID-19 Antiviral Remdesivir Multiplied 10-Fold by Hepatitis C Drugs

Remdesivir, the only antiviral drug approved in the United States for treating COVID-19 patients, is up to 10 times more effective when it is mixed with a repurposed hepatitis C drug. The effect has been observed with several hepatitis C drugs—namely, simeprevir, grazoprevir, paritaprevir, and vaniprevir. All four appear to have the same remdesivir-boosting mechanism: inhibition of the SARS-CoV-2 papain-like protease (PLpro).

These findings come from a study led by Adolfo García-Sastre, PhD, Robert M. Krug, PhD, and Gaetano T. Montelione, PhD, scientists affiliated with the Icahn School of Medicine at Mount Sinai, the University of Texas (UT) at Austin, and the Rensselaer Polytechnic Institute (RPI), respectively. Each of these scientists is listed as a corresponding author of a paper (“Hepatitis C Virus Drugs That Inhibit the SARS-CoV-2 Papain-Like Protease Synergize with Remdesivir to Suppress Viral Replication in Cell Culture”) published this week in Cell Reports.

According to the article, the three scientists and their colleagues tested 10 hepatitis C virus (HCV) protease-inhibitor drugs, some of which are already approved by the FDA, as potential SARS-CoV-2 antivirals. This work explored a possibility that had been raised earlier by RPI scientists. Specifically, they had identified a “striking similarity” between protease structures, or enzymes that are essential for coronaviral replication, in SARS-CoV-2 and HCV. The similarity suggested that existing drugs known to bind to and block the hepatitis C protease might have the same effect against SARS-CoV-2.

Using a supercomputer to model how drugs bind to viral proteins, the RPI researchers predicted that the 10 HCV drugs could bind snugly to the SARS-CoV-2 Main protease, named Mpro. In addition, they showed that seven of these drugs actually inhibited the SARS-CoV-2 protease.

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