Hepatitis C virus drugs that inhibit SARS-CoV-2 papain-like protease synergize with remdesivir to suppress viral replication in cell culture

• DOI: 10.1016/j.celrep.2021.109133
• Publication Date: 2021-04-27T05:28:29Z
• Authors: Khushboo Bafna; Kris White; Balasubramanian H...; 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. Montel...
• Keywords: NS3; Vero cell; NS2-3 protease; Protease inhibitor (pharmacology); Coronavirus

Effective control of COVID-19 requires antivirals directed against SARS-CoV-2. We assessed 10 hepatitis C virus (HCV) protease-inhibitor drugs as potential SARS-CoV-2 antivirals. There is a striking structural similarity the substrate binding clefts main protease (Mpro) and HCV NS3/4A protease. Virtual docking experiments show that these can potentially bind into Mpro substrate-binding cleft. seven inhibit both activity replication in Vero and/or human cells. However, their inhibiting activities did not correlate with antiviral activities. This conundrum resolved by demonstrating four inhibitor drugs, simeprevir, vaniprevir, paritaprevir, grazoprevir SARS CoV-2 papain-like (PLpro). PLpro synergize viral polymerase remdesivir to replication, increasing remdesivir's much 10-fold, while those only do remdesivir.