Fig. 2: EDP-235 is efficacious in a prophylactic Syrian hamster model.

a Study design. Hamsters were orally dosed with EDP-235 or vehicle 1 h prior to intranasal inoculation with 6\(\times\)10³ TCID₅₀/animal SARS-CoV-2 USA/WA1/2020 or PBS for naïve. b Percent body weight change from 0-day baseline (n = 8 per cohort). c IHC staining of terminal lung samples for SARS-CoV-2 N protein (brown) (2X magnification). Minimal focal immunoreactivity seen in 200 mg/kg animal (arrow). Representative images shown (n = 8 per cohort). d Sections of panel C were scored from 1 (minimal/minor) to 5 (severe/overwhelming) (n = 8 per cohort). e H&E stain of terminal lung samples (1.25X magnification). SARS-CoV-2 effects characterized by dark consolidated lung regions (arrows). Representative images shown (n = 8 per cohort). f Left lung composite histopathology score. Microscopic finding categories were alveolar hemorrhage, alveolar/interstitial inflammation, vascular inflammation, bronchial-alveolar hyperplasia, perivascular edema, and immunoreactivity. Each variable scored from 1-5 as in (d) (n = 8 per cohort). g Infectious virus titer in terminal lung samples (n = 8 per cohort). h sgRNA (N protein) in terminal lung samples (n = 8 per cohort). i) gRNA (N protein) in terminal lung samples (n = 8 per cohort). All graphs are mean ± SEM; statistical significance determined versus infected VC by 2-way ANOVA with Tukey’s (b) or 1-way ANOVA with Dunnett’s (d, f, g, h, i) post hoc test. All P values were < 0.0001 unless indicated otherwise in the figure. ANOVA = analysis of variance; g/sgRNA = genomic/sub-genomic RNA; h = hour; H&E = hematoxylin and eosin; IHC = immunohistochemistry; LoD = Limit of Detection; N protein = nucleocapsid protein; PBS = phosphate buffered saline; sac. = sacrifice; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SEM = standard error of the mean; TCID₅₀ = median tissue culture infectious dose; VC = vehicle control.