Fig. 6. A single dose of N-0385 reduces weight loss and viral burden in K18-hACE2 mice infected with the SARS-CoV-2 B.1.617.2 (Delta) VOC.
a, Weight change in K18-hACE2 mice treated once with saline at 12 hpi. b, Weight change in mice treated once with N-0385 at 12 hpi (14.4 mg kg−1). c, Weight change in mice treated once with N-0385 at 0 hpi (7.2 mg kg−1). d, Differences in weight loss across three treatment groups (a–c) at 6 dpi (n = 10 mice per treatment group); **P = 0.0012; ****P ≤ 0.0001. One-way ANOVA using Dunnett’s multiple comparisons test was used to assess significance. Data are mean ± s.d. e, Virus titres (PFU per g of tissue) from the lungs of infected mice 3 dpi. Titres were significantly lower for the N-0385 group compared to the saline control group; **P = 0.0081. Two-tailed Mann Whitney test was used to determine significance. Data are mean ± s.d., n = 10 mice per group. Plaque assays were performed twice per sample from each mouse and the average was used to determine the PFU per g. f, Numbers of events per mm2 that were positive for SARS-CoV-2 nucleocapsid (N) by IHC staining in lung tissue at 3 dpi; the reduction in positive cells was significantly greater for the N-0385 treatment versus the saline control; *P = 0.0355. Two-tailed Mann–Whitney test was used to determine significance. Data are mean ± s.d. One whole lung section was analysed per mouse (n = 10 mice per group). g, Total lung pathology scores of infected mice at 3 dpi as assessed on IHC were improved by approximately 1.9-fold (or 46%) and approach statistical significance; P = 0.053. Two-tailed Mann–Whitney test was used to determine significance Data are mean ± s.d. One complete lung section per mouse was analysed (n = 10 mice per group).