Fig. 5: Prophylactic efficacy of ZCB11 against authentic SARS-CoV-2 Delta and Omicron BA.1 in golden Syrian hamsters as compared with ZB8.

a Experimental schedule and color coding for different treatment groups. Three groups of male hamsters (n = 8) received a single intraperitoneal injection of PBS (gray), 4.5 mg/kg of ZB8 (purple) or 4.5 mg/kg of ZCB11 (blue) at one day before viral infection (−1 dpi). Twenty-four hours later (day 0), each group was divided into two subgroups for intranasal challenge with 10⁵ PFU live SARS-CoV-2 Delta and Omicron BA.1 variants, respectively. All animals were sacrificed on day 4 for final analysis. b, g Daily body weight change of each group (n = 4) was measured after viral infection. The data was shown as mean ± SEM. c, e, h, j The NP subgenomic RNA copy numbers (normalized by β-actin) in lung and nasal turbinate (NT) homogenates of each group (n = 4) were determined by a sensitive RT-PCR. The detection of viral load was performed in triplicates. d, f, i, k Live viral plaque assay was used to quantify the number of infectious viruses in lung and NT homogenates of each group (n = 4). Log10-transformed PFU per mL were shown for each group. The dash line indicates the limit of detection. l Representative histopathology of the lung tissues from pre-treated hamsters (n = 4 per group) after viral challenge. Tissue sections were stained with hematoxylin and eosin (H&E). In PBS-treated male hamsters, both Delta and Omicron could cause lung damages with alveolar septa thickening (black arrow), extensive inflammatory cell accumulation (blue arrow), homogeneously pink foci of edema (green arrow), and multifocal hemorrhage (red arrow). The scale bar represents 100 μm. PFU plaque-forming unit, SEM standard error of the mean, NP nucleocapsid protein, NT nasal turbinate, LOD limit of detection. Each symbol in c–f and h–k represents an individual hamster with a line indicating the mean of each group (n = 4). The color coding was consistently used in each graph. Statistics were generated using one-way ANOVA followed by Tukey’s multiple comparisons test. P-values were shown on each graph where necessary. Source data (b–j) are provided as a Source Data file.