University of California, Irvine Coronavirus Inhibitor-1 (UCI1-) is a cyclic peptide inhibitor that mimics the conformation of an Mpro substrate and binds at the C-terminal autolytic cleavage site of Mpro. UCI-1 can inhibit Mpro in vitro and is non-toxic to human cells in culture.

The main protease (Mpro or 3CL protease) is a member of a class of homologous cysteine proteases that are needed for viral replication in coronavirus caused diseases such as severe acute respiratory syndrome (SARS)-CoV and SARS CoV-2 and Middle East respiratory syndrome (MERS) and therefore represents a key drug target for coronaviruses.

UCI-1 contains amino acid side chains from the P2, P1, P1’, and P2’ positions of the Mpro substrate that are designed to fill the S2, S1, S1’, and S2’ pockets of the Mpro active site. UCI-1 acts as an inhibitor against Mpro and lays the groundwork for developing further cyclic peptide inhibitor analogues of UCI-1.

The molecule provided here is the linear form of UCI-1. This acts as a useful control for understanding the function of cyclic UCI-1 as the linear form is deisgned to not inhibit Mpro activity.