CMX990 is a potent, selective and covalent SARS-CoV-2 3CLpro inhibitor with IC50 of 23.4 nM, exhibits good potency (EC50=37 nM) in HeLa-ACE2 SARS-CoV-2 assays.
CMX990 displays in vitro activity in a HeLa-ACE2 cell culture model of SARS-CoV-2 infection provided a mean antiviral EC50/90 of 37/90 nM, with no detectable cytotoxicity.
CMX990 displays no activity against human peptidase selectivity panel, Cathepsin B/K/L/L2/S (All IC50>1 uM).
CMX990 potently and reproducibly inhibits the replication of eight SARS-CoV-2 variants tested, including alpha, delta, and omicron.
CMX990 also shows activity versus other betacoronaviruses (e.g., HCoV-OC43) as well as alphacoronaviruses (e.g., HCoV-229E) in live virus assays.
CMX990 performs 5× superior to nirmatrelvir in ALI-HBECs with a EC50/90 = 5.3/9.6 nM, having up to a 3-log reduction in viral load (72 h post-infection) when treated at 370 nM.