Combining Remdesivir and Hepatitis C Drugs May Give COVID-19 Treatment a Boost

Over a year after the onset of the pandemic, remdesivir remains the only drug approved for treating severe cases of COVID-19. Now preliminary research finds remdesivir's effectiveness may be dramatically improved by combining it with drugs used to treat hepatitis C.

Researchers at Rensselaer Polytechnic Institute (RPI), the University of Texas at Austin, and the Icahn School of Medicine at Mount Sinai found that four drugs used against hepatitis C—simeprevir, vaniprevir, paritaprevir, and grazoprevir—boosted the effectiveness of remdesivir tenfold. The April study was published in the journal Cell Reports.

One caveat: Researchers have only studied this combination treatment in cells, not humans. Although the drugs being studied for use with remdesivir have been approved by the Food and Drug Administration (FDA) for treating people with hepatitis C, it is not known if the combination will be effective against COVID-19 in humans. Clinical trials in humans will need to be conducted to determine if the combination is both safe and effective.

However, if this finding holds true in human clinical trials, the combination of intravenous remdesivir and an oral hepatitis C drug could be a useful treatment for people infected with SARS-CoV-2, the virus that causes COVID-19, and for vaccinated people whose immunity has waned, according to the researchers.

“I think clinical trials should be started immediately,” study co-author Robert M. Krug, PhD, professor emeritus in the department of molecular biosciences at the University of Texas at Austin, tells Verywell.

How it Works

Remdesivir was approved by the FDA for treatment of severe COVID-19 in October of last year, becoming the first FDA-approved drug for the virus. But the treatment itself is a repurposed antiviral drug, originally developed to treat hepatitis C, Ebola virus disease, and other viral infections. 

It targets a part of the SARS-CoV-2 virus called RNA polymerase, inhibiting the virus from replicating. Because both remdesivir and the hepatitis C drugs are already approved by the FDA, their side effects and potential adverse reactions are already known. 

However, the cell culture studies suggest that significantly higher doses of the oral hepatitis C drugs may need to be used in combination with remdesivir to boost efficacy; doses much higher than the amounts used to treat hepatitis C, study coauthor Kris White, PhD, in the microbiology department at the Icahn School of Medicine at Mount Sinai, tells Verywell. The dosage of the oral drugs may not have to be as high in humans, “but the only way to resolve that is to do the clinical trial,” he says.

Researchers at Mount Sinai are now testing the combined treatment in mice, White says, and are discussing the potential for clinical trials.

Repurposing Hepatitis C Drugs

When researchers first began considering combining these drugs to treat COVID-19, they noted there was a similarity in the structures of enzymes called proteases in both SARS-CoV-2 and hepatitis C. Using computer models, they tested the drugs that block the protease in hepatitis C to see if they bound to a protease called M^pro in SARS-CoV-2. Their computer model predicted that seven hepatitis drugs might work. But although the drugs inhibited replication of SARS-CoV-2, that inhibition did not correlate with antiviral activities.

Researchers then tested the seven drugs in cell cultures. To their surprise, simeprevir, vaniprevir, paritaprevir, and grazoprevir, which inhibit a different protease in SARS-CoV-2, called PL^pro, did work, and were effective antivirals.

Because remdesivir is an intravenous drug that needs to be administered daily, its use is limited to COVID-19 patients who have been hospitalized, Krug notes. If an oral drug that inhibits the virus’s polymerase can be created, combination treatment could be used on patients before they become so sick they require hospitalization.

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