Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19
O’ Brien, M.N.
AffiliationDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Arizona
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CitationBoras, B., Jones, R. M., Anson, B. J., Arenson, D., Aschenbrenner, L., Bakowski, M. A., Beutler, N., Binder, J., Chen, E., Eng, H., Hammond, H., Hammond, J., Haupt, R. E., Hoffman, R., Kadar, E. P., Kania, R., Kimoto, E., Kirkpatrick, M. G., Lanyon, L., … Allerton, C. (2021). Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19. Nature Communications.
RightsCopyright © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License.
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AbstractCOVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment. © 2021, The Author(s).
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Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License.