Figure 4. Efficacy of Nanosota-1 in protecting both hamsters and mice from SARS-CoV-2 infections.

(A, B) Hamsters (six per group) were injected with a single dose of Nanosota-1C-Fc at the indicated time point and the indicated dosage. At day 0, all groups (experimental and control) were challenged with SARS-CoV-2 (at a titer of 10⁶ Median Tissue Culture Infectious Dose [TCID₅₀]). (A) Body weights of hamsters were monitored on each day and percent change in body weight relative to day 0 was calculated for each hamster. Data are the mean ± SEM (n = 6). Analysis of variance (ANOVA) on group as a between-group factor and day (1-10) as a within-group factor revealed significant differences between the control group and each of the following groups: 24-hr pre-challenge (20 mg/kg) group (F(1, 10) = 17.80, p = 0.002; effect size η_p² = 0.64), 4-hr post-challenge (20 mg/kg) group (F(1, 10) = 5.02, p = 0.035; η_p² = 0.37), and 4-hr post-challenge (10 mg/kg) group (F(1, 10) = 7.04, p = 0.024; η_p² = 0.41). All p-values are two-tailed. (B) Tissues of bronchial tubes from each of the hamsters were collected on day 10 and scored for the severity of bronchioloalveolar hyperplasia: 3 - moderate; 2 - mild; 1 - minimum; 0 - none. Data are the mean ± SEM (n = 6). A comparison between the control group and each of other groups was performed using one-tailed Student’s t-test for directional tests. ***p<0.001; *p<0.05. (C, D) Human ACE2-transgenic mice (seven per group) were injected with a single dose of Nanosota-1C-Fc at the indicated time point and the indicated dosage. At day 0, all groups (experimental and control) were challenged with SARS-CoV-2 (at a titer of 5 x 10³ plaque-forming unit [PFU]). (C) Five mice from each group were euthanized on day 2 post-challenge, and the virus titers in their lungs were measured using a plaque assay. A comparison between the control group and each of the other groups was performed using one-tailed Student’s t-test for directional tests. Data are the mean ± SEM (n = 5). **p<0.01; *p<0.05. (D) The remaining two mice from each group were euthanized on day 5 post-challenge. Lung tissues were collected and examined for pathological changes after staining with hematoxylin and eosin. Phosphate-buffered saline (PBS) control group: severe inflammatory cell infiltration and bronchiole infiltration on the top panel; severe alveolar edema filled with liquid (labeled *) and proliferative alveolar epithelium (labeled →) on the bottom panel. 24-hr pre-challenge 20 mg/kg group: close to normal. 24-hr pre-challenge 10 mg/kg group: minor proliferative alveolar epithelium and inflammatory cell infiltration. 4-hr post-challenge 20 mg/kg group: close to normal. 4-hr post-challenge 10 mg/kg group: obvious cell inflammatory cell infiltration and vascular thrombosis (labeled #).