Extended Data Fig. 10: In vivo suppression of DOCK2 in a Syrian hamster model with SARS-CoV-2 infection.

(a) Schematic timeline of the experimental procedure. (b) Changes in weight of uninfected animals. The error bars represent standard error of the mean. (c) Changes in weight of each of the infected animals, corresponding to Fig. 3a. Three CPYPP-administrated animals reaching humane endpoint were euthanized at dpi 7 and 9, lowering survival rate to 77% (=10/13), while survival of vehicle-administrated animals was 100% (=12/12). The animals were administered with CPYPP (red), or vehicle (blue). (d) Histopathological examination of the lungs of infected hamsters. Syrian hamsters were inoculated with SARS-CoV-2 with CPYPP or Vehicle. Syrian hamsters infected with CPYPP or Vehicle were euthanized on dpi 3, 6, and 11 for pathological examinations (n = 3). Shown are pathological findings in the lungs of hamsters infected with the virus on dpi 3, 6, and 11 (hematoxylin and eosin staining). Middle and Right show enlarged views of the area circled in black in Left. (Scale bars, 2.5 mm [Left], 1.0 mm [Middle], and 0.25 mm [Right].) (e) Immunohistochemistry for alveolar macrophages. Shown are immunohistochemical findings in the lungs of hamsters infected with the virus on dpi 6 (n = 3 per group). Lung tissue was stained with the anti-CD68 mouse monoclonal antibody. (Scale bars, 0.25 mm.) (f) Pathological severity scores in infected hamsters. To evaluate comprehensive histological changes, lung tissue sections were scored based on (d) pathological changes. Scores were determined based on the percentage of inflammation area of the maximum cut surface collected from each animal in each group by using the following scoring system: 0, no pathological change; 1, affected area (≤10%); 2, affected area (<50%, > 10%); 3, affected area (<90%, ≥50%); 4, (≥90%) an additional point was added when pulmonary edema and/or alveolar hemorrhage was observed. The total score is shown for individual animals. Blue dot and red dot indicate +Vehicle and +CPYPP, respectively.