Repurposing the HCV NS3-4A protease drug boceprevir as COVID-19 therapeutics

Rick Oerlemans, Angel Ruiz Moreno, Ying-Ying Cong, Nilima Dinesh Kumar, M.A. Velasco-Velazquez, Constantinos G. Neochoritis, Jolanda Smit, Fulvio Reggiori, Matthew Groves, Alex Dömling*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

52 Citaten (Scopus)
65 Downloads (Pure)


The rapid growth of COVID-19 cases is causing an increasing death toll and also paralyzing the world economy. De novo 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.

Originele taal-2English
Pagina's (van-tot)370-379
Aantal pagina's10
TijdschriftRSC Medicinal Chemistry
Nummer van het tijdschrift3
Vroegere onlinedatum21-dec.-2020
StatusPublished - 1-mrt.-2021

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