Download MendeleyRepurposing the HCV NS3-4A protease drug boceprevir as COVID-19 therapeutics.
Oerlemans, R., Ruiz-Moreno, A.J., Cong, Y., Dinesh Kumar, N., Velasco-Velazquez, M.A., Neochoritis, C.G., Smith, J., Reggiori, F., Groves, M.R., Domling, A.(2020) RSC Med Chem 12: 370-379
- PubMed: 34041486
- DOI: https://doi.org/10.1039/d0md00367k
- Primary Citation of Related Structures:
6ZRT, 6ZRU - PubMed Abstract:
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.
Organizational Affiliation:
Department of Drug Design, University of Groningen The Netherlands [email protected].
