PF-00835231 (PF00835231) is a potent inhibitor of pan-coronavirus family 3CL pro (IC50=0.27 nM, SARS CoV-2), with selectivity over human host protease targets.
PF-00835231 inhibits SARS CoV-1 3CL pro with IC50 of 4 nM, displaying IC50 values of >10 μM against many of the other proteases and possessing modest levels of inhibition of cathepsin B (IC50 = 1.3 μM) and rhinovirus 3Cpro (IC50 = 1.7 μM).
PF-00835231 demonstrated potent inhibitory activity against all tested coronavirus 3CLpro including members of alpha-coronaviruses (NL63-CoV, HCoV-229E, PEDV, FIPV), beta-coronaviruses (HKU4-CoV, HKU5-CoV, HKU9-CoV, MHV-CoV, OC43-CoV, HKU1-CoV), and gamma-coronavirus (IBV-CoV), with Ki values ranging from 30 pM to 4 nM.
PF-00835231 exhibited viral effect against SARS-CoV-2 in cell culture, also showed potential synergy with remdesivir in HeLa-ACE2 cells.
PF-00835231 demonstrateed in vivo effect in mouse models of SARS-CoV and SARS-CoV-2 infection.