TY - JOUR T1 - Structure-Based Design of a Cyclic Peptide Inhibitor of the SARS-CoV-2 Main Protease JF - bioRxiv DO - 10.1101/2020.08.03.234872 SP - 2020.08.03.234872 AU - Adam G. Kreutzer AU - Maj Krumberger AU - Chelsea Marie T. Parrocha AU - Michael A. Morris AU - Gretchen Guaglianone AU - James S. Nowick Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/08/05/2020.08.03.234872.abstract N2 - 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.Competing Interest StatementThe authors have declared no competing interest. ER -