ISM3312 is a potent, irreversible covalent broad-spectrum inhibitor of human coronavirus main protease (Mpro) with IC50 of 14 nM, exhibits potent cellular potency in VeroE6 cell lines with EC50 of 71 nM.
ISM3312 effectively binds to a variety of CoV catalytic pockets without collision.
ISM3312 exhibited a broad and potent inhibition against Mpro derived from a panel of coronaviruses (Omicron P132H, SARS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1 and MERS-CoV) with IC50 of 4-52 nM.
ISM3312 exhibited potent antiviral efficacy against a spectrum of tested SARS-CoV-2 variants including the ancestral, Delta, BA.2.3, BA.5, XBB.1, and EG.5 with EC50 of 0.03-0.14 uM in VeroE6 CPE-based assays.
ISM3312 exhibited lower EC50s against the low pathogenicity coronavirus strains 229E, NL63, and OC43 than Nirmatrelvir and Ensitrelvir with EC50 values of 19, 167, and 56  nM, respectively.
ISM3312 exhibits potent antiviral activity against various coronaviruses in human proximal airway organoid model
ISM3312 inhibits a spectrum of CoVs in vivo, shows significant inhibitory effects against Nirmatrelvir-resistant Mpro mutants.