Hepatitis C drugs may inhibit main protease of SARS-CoV-2, aid in COVID-19 treatment, says study

New research published in the peer-reviewed journal Structure indicates that hepatitis C drugs may be able to inhibit the functioning of SARS-CoV-2 main protease and hence it could be used to treat COVID-19. Proteases are enzymes that can cut proteins into smaller fragments. Since COVID-19 is a new disease and the development of novel drugs takes a lot of time, scientists have been studying several pre-existing drugs for the treatment of the disease. Anti-inflammatory drugs like hydroxychloroquine, steroids like dexamethasone and nucleoside analogous like remdesivir are already in research or have shown to be effective. However, experts are still continuously looking for better and quicker ways to manage the disease, prevent mortality and reduce overburdening of healthcare facilities. The latest study, done at the DOE/Oak Ridge National Laboratory, USA, adds another to the list of drugs that are being studied for COVID-19 treatment. The study For the study, the researchers used X-ray crystallography technique to assess the binding capacity of various drugs with the main protease called Mpro of SARS-CoV-2. The drugs included three FDA approved hepatitis C drugs - telaprevir, narlaprevir and boceprevir. Another protease inhibitor called leupeptin was also included in the study. Mpro is an established drug target for COVID-19. The enzyme breaks down the long-chain of polyproteins (chains of proteins) into individual proteins that then perform various functions in the viral life-cycle. So, inhibiting its function would keep the virus from functioning properly. As per the latest study, the stronger the binding efficiency of a compound with the enzyme, the better it would inhibit its activity. As the researchers observed a weak binding affinity of leupeptin with Mpro, the drug was taken out of the study. On the other hand, the hepatitis C drugs telaprevir, narlaprevir and boceprevir were able to better bind with the enzyme. The study also indicated the specific way all of these compounds bind with Mpro and how it reshapes the active site of the enzyme. The active site is a pocket in enzymes which binds to specific substrates (the molecules that the said enzyme normally binds to and acts on). Explaining the findings of the study, Dr Andrey Kovalevsky, the corresponding author of the study, said in a news release by the DOE/Oak Ridge National Laboratory, “What we’re doing is laying the molecular foundation for these potential drug repurposing inhibitors by revealing their mode of action.” “You can’t design a drug without knowing how it works on a molecular level, and the data we’re providing is exactly what developers need to design stronger, more tightly binding drugs for more effective treatments,” added Dr Leighton Coates, another corresponding author. Not the first study Several studies have previously indicated the efficiency of Mpro inhibitors in the treatment of COVID-19. A study done in Canada has previously indicated that GC376, a prodrug used to treat cat coronavirus, has broad-spectrum activity against the Mpro in coronaviruses. In another study, a group of compounds called calpain inhibitors were found to be more effective against SARS-CoV-2 Mpro than even GC376. Additionally, two drugs called disulfiram and neratinib that are used for the treatment of alcoholism have also been proposed to be effective against Mpro in the novel coronavirus. However, more studies are still needed to find the right Mpro inhibitor and get it approved for COVID-19 treatment. For more information, read our article on Hepatitis C. Health articles in Firstpost are written by myUpchar.com, India’s first and biggest resource for verified medical information. At myUpchar, researchers and journalists work with doctors to bring you information on all things health.