Scientists from the University of Texas at Austin, Rensselaer Polytechnic Institute (RPI), and the Icahn School of Medicine at Mount Sinai in the USA have found that hepatitis C virus (HCV) protease-inhibitor drugs can inhibit SARS-CoV-2 and work effectively alongside remdesivir. The repurposed drug remdesivir inhibits the viral RNA-dependent polymerase, which facilitates the virus’s replication in host cells. Meanwhile, the HCV drugs target two other parts of SARS-CoV-2, called proteases.
These are also crucial for viral replication. The researchers found similarities between the structures of HCV protease (NS3A/) and SARS-CoV-2 main protease (Mpro). Using virtual molecular docking experiments ten HCV protease inhibitors were identified. The team found that seven drugs inhibited SARS-CoV-2 Mpro protease activity and SARS-CoV-2 virus replication in cell cultures. The researchers noted that four HCV drugs – vaniprevir, simeprevir, grazoprevir, and paritaprevir – inhibited a new type of SARS-CoV-2 protease, known as papain-like protease.
Their results indicated that the SARS-CoV-2 PLpro is an important target for future antiviral drug development when used in conjunction with polymerase inhibitors, could provide potent efficacy and protection from SARS-CoV-2 especially for virus variants that are resistant to vaccine generated antibodies.
Ref Link: https://doi.org/10.1016/j.celrep.2021.109133