Sorrento Therapeutics, Inc. announced its late-stage preclinical Mpro inhibitor, STI-1558, effectively inhibits Omicron virus entry and replication in cell-based assays. The world is experiencing a huge wave of infection with the Omicron variant of SARS-CoV-2, and current vaccines and EUA-approved antibodies offer diminished protection against Omicron transmission and infection. STI-1558 is an oral Mpro inhibitor which has demonstrated in preclinical studies broad-spectrum anti-SARS-CoV-2 activity when tested for activity against the original SARS-CoV-2 strain and all previous predominant variants of concern (VOCs).

STI-1558's antiviral activity against Omicron has also been tested in a cell-based neutralization assay. In VeroE6 cells challenged with Omicron variant, STI-1558 alone (without efflux inhibitor) showed significant antiviral activity with an EC50 value of 360 nM, equivalent activity to that seen against the Delta variant (EC50 value, 370 nM). Notably, in an Omicron S protein-mediated pseudovirus entry assay, STI-1558 effectively inhibited pseudovirus entry into cells, whereas EUA-approved nirmatrelvir showed no inhibition.

Particularly, STI-1558 showed improved human liver metabolic stability as compared to nirmatrelvir, and its oral bioavailability does not depend on the ritonavir co-administration. Without the need to co-administer Ritonavir, STI-1558 potentially avoids significant adverse drug-drug interactions.