NZ-804 is a potent, selective, non-peptidic, non-covalent inhibitor of SARS-CoV-2 main protease (Mpro) with IC50 of 9 nM and antiviral EC50 of 14 nM.
NZ-804 has potent and broad activity against the CoV family, exerts antiviral activity against pandemic, epidemic, endemic, and enzootic CoVs, including pandemic SARS-CoV-2 D614G (NZ-804 EC50 = 0.009 μM, Nirm EC50 = 0.03 μM); SARS-CoV-2 WA1 (NZ-804 EC50 = 0.01 μM); SARS-CoV-2-like pangolin CoV PgCoV (NZ-804 EC50 = 0.006 μM, Nirm EC50 = 0.02 μM); SARS-CoV-like bat CoV WIV1 (NZ-804 EC50 = 0.002 μM, Nirm EC50 = 0.02 μM), and SARS-CoV-like bat CoV SHC014 (NZ-804 EC50 = 0.007 μM, Nirm EC50 = 0.03 μM).
NZ-804 does not select for specific resistance in SARS-CoV-2. NZ-804 retains inhibition of mutant Mpro enzyme that is resistant to Nirm (Paxlovid).
NZ-804 effectively reduced SARS-CoV-2 replication and pathogenesis, reduces SARS-CoV-2 replication and pathogenesis in mice.