publication . Article . 2021

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

Rick Oerlemans; Angel J Ruiz-Moreno; Yingying Cong; Nilima Dinesh Kumar; Marco A. Velasco-Velázquez; Constantinos G. Neochoritis; Jolanda Smith; Fulvio Reggiori; Matthew Groves; Alexander Dömling;
Open Access English
  • Published: 01 Mar 2021
  • Country: Netherlands
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.
α-Ketoamide HCV protease inhibitors covalently bind to SARS-CoV-2 3CLpro. Boceprevir is a particular promising repurposed drug as it potently inhibits cellular viral proliferation.
Fields of Science and Technology classification (FOS)
03 medical and health sciences, 0301 basic medicine, 030302 biochemistry & molecular biology, 030304 developmental biology
Sustainable Development Goals (SDG)
3. Good health
Medical Subject Headings: virus diseasesviruses
free text keywords: Chemistry, Organic Chemistry, Drug Discovery, Pharmaceutical Science, Pharmacology, Molecular Medicine, Biochemistry, Drug repositioning, Telaprevir, medicine.drug, medicine, Repurposing, Boceprevir, chemistry.chemical_compound, chemistry, business.industry, business, Protease, medicine.medical_treatment, Coronavirus, medicine.disease_cause, Drug discovery, Drug, media_common.quotation_subject, media_common, Virology
  • COVID-19
Funded by
Driving next generation autophagy researchers towards translation
  • Funder: European Commission (EC)
  • Project Code: 765912
  • Funding stream: H2020 | MSCA-ITN-ETN
Protecting patients with enhanced susceptibility to infections
  • Funder: European Commission (EC)
  • Project Code: 713660
  • Funding stream: H2020 | MSCA-COFUND-DP
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Open Access
Article . 2021
Providers: NARCIS
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