EDP-235 (Zevotrelvir, EDP235) is a potent, selective inhibitor of SARS-CoV-2 3CLpro with IC50 of 4.0 nM, Kiapp of 3.0 nM, reversibly binds and inhibits the 3CLpro.
EDP-235 shows weak inhibition (IC50 ≥ 2 µM) of mammalian cysteine proteases and an excellent selectivity index (SI) ≥ 500-fold, has no cytotoxicity was detected in Vero E6, HuH-7, Madin-Darby canine kidney, A549-ACE2, MRC5, or HeLa cells.
EDP-235 has potent antiviral activity against SARS-CoV-2 with EC50 of 4.5 nM in SARS-CoV-2 replicon system. inhibited CPE and virion production with EC50S ranging from 11-22 nM and 3-7.4 nM, in the absence and presence of PGPi CP-100356, respectively, in Vero E6 cells infected with ancestral (A: SARS-CoV-2 USA-WA1/2020), B (Germany/BavPat1/2020), Delta (B.1.617.2), or Omicron (B.1.1.529) strains.
EDP-235 inhibits multiple SARS-CoV-2 Omicron variants of interest with EC50s ranging from 10 to 73 nM.
EDP-235 inhibits viral replication, as quantified by 50% tissue culture infectious dose (TCID50), of SARS-CoV-2 lineage B with EC50/90 values of 29/33 nM, respectively, using primary human airway epithelial cells maintained at an air-liquid interface (pHAEC-ALI).
EDP-235 maintains activity against known SARS-CoV-2 nirmatrelvir-resistant variants.
EDP-235 is a pan-coronavirus inhibitor, inhibits the replication of HCoV-229E ( < 10 nM EC50s in multiple assay formats), HCoV-OC43 (57 nM EC50), HCoV-HKU1 (3.8 nM IC50), and HCoV-NL63 (6.1 nM EC50). also shows activity against each of the infectious zoonotic viruses (EC50 6.9-21 nM).
EDP-235 (200 mg/kg twice daily (BID), 500 mg/kg BID) is efficacious in a SARS-CoV-2 hamster model, EDP-235 effectively blocks infection and viral transmission in ferrets.