Fig. 6.
Efficacy of ZCP3B4 in preventing authentic Omicron BA.5.2, BQ.1.1 and XBB.1.5 transmission in golden Syrian hamsters. (A) Experimental schedule and color coding for different treatment groups. Index hamsters (male, n = 6) were challenged intranasally with a mixture of live Omicron BA.5.2, BQ.1.1 and XBB.1.5 (105 PFU/hamster) two days prior to the co-housing (day 0). On 2 dpi, two groups of male hamsters were administered intranasally with PBS (n = 6) or 4.5 mg/kg of ZCP3B4 (n = 6) 8 h before being co-housed with index hamsters at a 2:1 ratio. 4 h after the co-housing, index hamsters were sacrificed, whereas PBS- and ZCP3B4-treated hamsters were separated and sacrificed on day 4 for final analysis. (B) Live viral plaque assay was used to quantify the number of infectious viruses in lungs and nasal turbinate (NT) homogenates of each group. Log10-transformed plaque-forming unit (PFU) per mL was shown for each group. The dash line indicates the limit of detection. Each symbol represents an individual hamster with a line indicating the mean of each group. Statistics were generated using one-way ANOVA followed by Tukey's multiple comparisons test. ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001. (C) Representative histopathology of lung tissues and NT from index and pre-treated hamsters after the co-housing. Tissue sections were stained with hematoxylin and eosin (H&E). For index and PBS-treated hamsters, the infection could cause lung damage with alveolar septa thickening (black arrow), extensive inflammatory cell accumulation (blue arrow), homogeneously pink foci of edema (green arrow), and multifocal hemorrhage (red arrow). In NT, submucosal immune cell accumulation (blue arrow) as well as damage to the respiratory and olfactory epithelium (black arrow) are also indicated. The resolution is indicated by the scale bar. (D) Representative images of infected cells in NT from index and pre-treated hamsters after the co-housing. Viral nucleocapsid protein (NP) was stained in green by immunofluorescence staining and cell nuclei were stained in blue with DAPI. The scale bar represents 100 μm.