Structure-Based Design of a Cyclic Peptide Inhibitor of the SARS-CoV-2 Main Protease
Adam G. Kreutzer, Maj Krumberger, Chelsea Marie T. Parrocha, Michael A. Morris, Gretchen Guaglianone, James S. Nowick · bioRxiv (Cold Spring Harbor Laboratory) · 2020
ABSTRACT This paper presents the design and study of a first-in-class cyclic peptide inhibitor against the SARS-CoV-2 main protease (M pro ). The cyclic peptide inhibitor is designed to mimic the conformation of a substrate at a C -terminal autolytic cleavage site of M pro . Synthesis and evaluation of a first-generation cyclic peptide inhibitor reveals that the inhibitor is active against M pro 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 M pro with improved activities.