Science News reported that a combination of remdesivir, a drug formulated by SBECD and currently approved in the United States for treating COVID-19 patients, and repurposed drugs for hepatitis C virus (HCV) was 10 times more effective at inhibiting SARS-CoV-2, the virus that causes COVID-19.
Using a supercomputer to model how drugs bind to viral proteins, the 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. The research team then tested whether these seven drugs would inhibit SARS-CoV-2 virus replication in monkey and human cells grown in culture. In subsequent experiments the researchers were surprised to find that the four HCV drugs inhibited a different SARS-CoV-2 protease, known as PLpro. This observation proved to be very important. When each of the seven HCV drugs were tested in combination with remdesivir, only the four drugs (boceprevir (BOC), narlaprevir (NAR), vaniprevir (VAN), telaprevir (TEL), that unexpectedly targeted PLpro boosted the efficacy of remdesivir, by as much as 10-fold.
One big drawback of remdesivir is that it must be administered intravenously, limiting its use to patients already admitted to the hospital. It is important to identify oral drugs that inhibit the SARS-CoV-2 polymerase in order to develop an effective outpatient treatment.
Khushboo Bafna, Kris White, Balasubramanian Harish, Romel Rosales, Theresa A. Ramelot, Thomas B. Acton, Elena Moreno, Thomas Kehrer, Lisa Miorin, Catherine A. Royer, Adolfo García-Sastre, Robert M. Krug, Gaetano T. Montelione. Hepatitis C Virus Drugs That Inhibit the SARS-CoV-2 Papain-Like Protease Synergize with Remdesivir to Suppress Viral Replication in Cell Culture. Cell Reports, 2021; 109133 DOI: 10.1016/j.celrep.2021.109133