Extended Data Fig. 5. SARS-CoV-2 in the lungs of mice treated with N-0385 as demonstrated by IHC and plaque assay.
(A) Mice were treated daily on days −1 to +6 relative to challenge, with surviving mice terminated on Day 14 (same mice as Fig. 4). (B) Number of cells/mm2 positive for SARS-CoV-2 nucleocapsid (N) at time of death or end-point by IHC staining. One whole lung slice evaluated per mouse. Data presented are mean ± SD (C) Virus titers (plaque-forming unit (PFU)/g of tissue) from the lungs of infected mice at time of death or end-point. Plaque assays were performed twice using a sample from each mouse and the average used to determine PFU/g. Data presented are mean ± SD (D) Representative sections of SARS-CoV-2 N staining in the brains of SARS-CoV-2 infected mice at time of death or end-point. Mice treated with saline (a, b: day 8) often had positive immunoreactivity in neurons throughout the brain. Immunoreactivity for SARS-CoV-2 was rare to absent in mice that survived to the study end-point (c, d, e, f: day 14). (E) Representative sections of SARS-CoV-2 nucleocapsid in the lung of SARS-CoV-2-infected mice at time of death or end-point. Mice treated with saline (a, b: day 7) had immunoreactivity against SARS-CoV-2 throughout the lung. A similar pattern of patchy infection was present in mice treated with N-0385(OH) (c, d: day 6) but was not present in all mice. Immunoreactivity for SARS-CoV-2 was rare to absent in N-0385-treated mice that survived to the study end-point (e, f: day 14). Scale bar for D, E: a, c, e = 1 mm; b, d, f = 50 μm. For each experiment, 10 mice (5 males; 5 females) were analysed per treatment group. For histopathology and IHC analyses, representative images were selected based on the prevalent trend for a given treatment group, showing images representative of the mean pathological score