Repurposing the HCV NS3-4A Protease Drug Boceprevir As COVID-19 Therapeutics

Overview

Journal RSC Med Chem

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2021 May 27

PMID 34041486

Citations 43

Authors

Rick Oerlemans

Angel Jonathan Ruiz-Moreno

Yingying Cong

Nilima Dinesh Kumar

Marco A Velasco-Velazquez

Constantinos G Neochoritis

Jolanda Smith

Fulvio Reggiori

Matthew R Groves

Alexander Domling

Affiliations

Soon will be listed here.

Abstract

The rapid growth of COVID-19 cases is causing an increasing death toll and also paralyzing the world economy. drug discovery takes years to move from idea and/or pre-clinic to market, and it is not a short-term solution for the current SARS-CoV-2 pandemic. Drug repurposing is perhaps the only short-term solution, while vaccination is a middle-term solution. Here, we describe the discovery path of the HCV NS3-4A protease inhibitors boceprevir and telaprevir as SARS-CoV-2 main protease (3CLpro) inhibitors. Based on our hypothesis that α-ketoamide drugs can covalently bind to the active site cysteine of the SARS-CoV-2 3CLpro, we performed docking studies, enzyme inhibition and co-crystal structure analyses and finally established that boceprevir, but not telaprevir, inhibits replication of SARS-CoV-2 and mouse hepatitis virus (MHV), another coronavirus, in cell culture. Based on our studies, the HCV drug boceprevir deserves further attention as a repurposed drug for COVID-19 and potentially other coronaviral infections as well.

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