Fig. 4. Lung histopathological changes with preemptive or preventive favipiravir therapy.

Groups of four animals were intranasally infected with 10⁴ TCID₅₀ of virus and sacrificed at 3 and 5 dpi. Experimental timelines for preemptive (a) and preventive (c) favipiravir therapies. At day of sacrifice, lungs were collected, fixed, and embedded in paraffin. Tissue sections were stained with hematoxylin-eosin (H&E). Based on severity of inflammation, alveolar hemorrhagic necrosis, and vessel lesions, a cumulative score from 0 to 10 was calculated and assigned to a grade of severity (I, II, III, and IV). Scoring of pathological changes for preemptive (b) and preventive (d) favipiravir therapies (n = 4 animals/group) (details in Supplementary Data 7). Two-sided statistical analysis were performed using Shapiro–Wilk normality test, Student t-test, Mann–Whitney test, and two-way ANOVA with Post-hoc Dunnett’s multiple comparisons test (details in Supplementary Data 7 and 8). * Symbol indicates that the average value for the group is significantly different from that of the untreated group with a p-value ranging between 0.01 and 0.05. e Representative images of lung tissue (left lobe) (scale bar: 4 mm): multifocal and extensive areas of inflammation for untreated animal, multifocal but limited areas of inflammation for 37.5 mg/day treated animal and normal lung for 75 mg/day treated animal (n = 4 samples/group). f Representative images of bronchial inflammation (scale bar: 100 µ): severe peribronchiolar inflammation and bronchiole filled with neutrophilic exudates for untreated animal, mild peribronchiolar inflammation for 37.5 mg/day treated animal and normal bronchi for 75 mg/day treated animal (n = 4 samples/group). g Representative images of alveolar inflammation (scale bar: 100 µ): severe infiltration of alveolar walls, alveoli filled with neutrophils/macrophages for untreated animal, moderate infiltration of alveolar walls, some alveoli filled with neutrophils/macrophages for 37.5 mg/day treated animal and normal alveoli for 75 mg/day treated animal. h Representative images of vessel inflammation (scale bar: 50 µ): infiltration of vascular wall with neutrophils/cell debris and endothelial damage (arrow) for untreated animal, moderate endothelial leukocytic accumulation for 37.5 mg/day treated animal and normal vessel for 75 mg/day treated animal (n = 4 samples/group). Clinical courses of the disease are presented in Supplementary Fig. 6. Source data are provided as a Source data file.