US researchers have found that combining Remdesivir — a drug currently approved for treating Covid-19 patients — with repurposed drugs for hepatitis C virus (HCV) is 10 times more effective at slowing down SARS-CoV-2, the virus that causes coronavirus. The study, published in the journal Cell Reports, showed that four HCV drugs — Simeprevir, Vaniprevir, Paritaprevir, and Grazoprevir — in combination with Remdesivir boosted the efficacy of the drug by as much as 10-fold.
The combination therapy points a way toward a treatment for unvaccinated people who become infected, as well as for vaccinated people whose immunity has waned, for example, due to the emergence of virus variants that escape this immune protection, said the research team.
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“Because these HCV drugs are already approved for use and their potential side effects are known, such a combination therapy could be tested in humans more quickly than for a new drug,” said Robert M. Krug, Professor at the University of Texas. One drawback of Remdesivir is that it must be administered intravenously, limiting its use to patients already admitted to the hospital.
“Our goal is to develop a combination of oral drugs that can be administered to outpatients before they are sick enough to require hospitalization,” said Krug. “The HCV drugs that enhance Remdesivir’s antiviral activity are oral drugs. It is important to identify oral drugs that inhibit the SARS-CoV-2 polymerase in order to develop an effective outpatient treatment.”
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Using a supercomputer to model how drugs bind to viral proteins, the team predicted that 10 HCV drugs would bind snugly to a SARS-CoV-2 protease. The researchers tested seven of these drugs in a secure biocontainment facility for their ability to inhibit SARS-CoV-2 virus replication in monkey and human cells growing in culture.
All seven HCV drugs inhibited virus replication, but the team was surprised to find that four of them inhibited an entirely different type of SARS-CoV-2 protease, called the papain-like protease. And that difference proved to be important. When each of the seven HCV drugs was tested for virus inhibition in combination with Remdesivir, only the four that targeted the unexpected protease boosted the , by as much as tenfold, the team explained. (IANS/JC)