Extended Data Fig. 1: Microsomal stability, mouse and hamster PK parameters, CYP inhibition and in vivo efficacy of CIM-834.
From: A coronavirus assembly inhibitor that targets the viral membrane protein
a, Liver microsomal stability was determined as described in the materials and methods. For PK studies, CIM-834 was formulated as a solution in propylene glycol/Tween80/pH 5 citrate buffer (14/1/85) and administered to male CD-1 mice at 10 or 100 mg/kg, or administered to female hamsters at 100 mg/kg after a pre-treatment of ritonavir as a solution formulated in EtOH/propylene glycol/water (43/27/30) at 50 mg/kg. RoA: route of administration. CL, clearance; Vss, steady-state volume of distribution; Cmax, maximum concentration; AUClast, area under the curve up to the last measurable concentration. F was calculated based on AUClast iv and po and corrected for dose. ND: not determined. b, IC50 of CIM-834 on different CYP enzymes. c, SCID mice were intranasally infected with 105 TCID50 SARS-CoV-2 B.1.351 and treated orally once (QD) or twice (BID) daily with CIM-834 or nirmatrelvir. No ritonavir was used in either of the treated groups. Treatment was initiated just before infection. Lung infectious titres, vRNA and body weight change were determined 3 days post-infection (Kruskal-Wallis test and Dunn’s comparison, median values (infectious virus and vRNA) or mean ± s.d, (weight change), n = 2 biologically independent experiments with 6 mice in each group/experiment).
