Hep C Antivirals Can Potentiate Remdesivir Activity

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