Fig. 4.

Pathological findings in the lungs of rhesus macaques inoculated with MERS-CoV and treated with remdesivir. Three groups of six rhesus macaques were inoculated with MERS-CoV strain HCoV-EMC/2012; one group was i.v.-administered 1 mL/kg vehicle solution (vehicle control; gray circles), one group was administered 5 mg/kg remdesivir starting at 24 h before inoculation (prophylactic remdesivir; black squares), and one group was administered 5 mg/kg remdesivir starting at 12 h after inoculation (therapeutic remdesivir; red triangles). Treatment was continued once daily until 6 dpi, when all animals were euthanized and necropsies were performed. At necropsy, the percentage of each lung lobe affected by gross lesions was estimated by a board-certified veterinary pathologist (A). Lung samples were collected and stained with H&E and analyzed for the presence of lesions by a board-certified veterinary pathologist. Each lung was given a score from 0 to 4 based on the abundance of lesions; the cumulative histology score is the sum of the scores of the six individual lung lobes per animal (B). One representative H&E image was chosen for each group (magnification: 100×) (C). Lung samples were also stained with a polyclonal α-MERS-CoV antibody; one representative image was chosen for each group (magnification: 200×) (D). Images in C and D were chosen as representative images of lung lesions and antigen expression, respectively, rather than being images from consecutive tissue slides. Asterisks indicate statistically significant differences in a two-way ANOVA with Dunnett’s multiple comparisons. **P < 0.01; ****P < 0.0001.