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bioRxiv · 10.1101/2020.08.03.234872

Structure-Based Design of a Cyclic Peptide Inhibitor of the SARS-CoV-2 Main Protease

Kreutzer, A. G.·Krumberger, M.·Parrocha, C. M. T.·Morris, M. A.·Guaglianone, G.·Nowick, J. S.
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Abstract

This paper presents the design and study of a first-in-class cyclic peptide inhibitor against the SARS-CoV-2 main protease (Mpro). The cyclic peptide inhibitor is designed to mimic the conformation of a substrate at a C-terminal autolytic cleavage site of Mpro. Synthesis and evaluation of a first-generation cyclic peptide inhibitor reveals that the inhibitor is active against Mpro in vitro and is non-toxic toward human cells in culture. The initial hit described in this manuscript, UCI-1, lays the groundwork for the development of additional cyclic peptide inhibitors against Mpro with improved activities.

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Kreutzer, A. G., Krumberger, M., Parrocha, C. M. T., Morris, M. A., Guaglianone, G., Nowick, J. S.. 2020-08-03. Structure-Based Design of a Cyclic Peptide Inhibitor of the SARS-CoV-2 Main Protease. https://doi.org/10.1101/2020.08.03.234872

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