MR1-114

MR1-114 (also known as compound 15) is a next-generation, potent, noncovalent small molecule inhibitor of the SARS-CoV-2 papain-like protease (PLpro), developed by Sunshine Biopharma in collaboration with the University of Arizona. Discovered through structure-based drug design, MR1-114 incorporates a strategic alkyne linker designed to access the cryptic Val70^Ub binding pocket and the BL2 groove, which are remote from the catalytic site. This design drives high cellular potency and broad-spectrum activity against multiple SARS-CoV-2 variants of concern, including Delta and Omicron BA.5. Preclinical studies demonstrate a favorable ADME profile with high solubility, permeability, hepatocyte stability, high oral bioavailability across multiple species, and preferential lung enrichment. In the K18-hACE2 mouse model, oral administration of MR1-114 matched the therapeutic efficacy of nirmatrelvir (Paxlovid), significantly suppressing pulmonary viral replication and preventing disease-associated weight loss. The compound has advanced into IND-enabling studies for the treatment of SARS Coronavirus infections.

Other names

MR1 114MR-1 114MR 1 114MR1114MR-1114MR 1114compound 15compound15compound-15