Fig. 5: Therapeutic efficacy of 6L3-1F3P11hR in SARS-CoV-2-infected K18-hACE2 transgenic mice.
a Schematic of the in vivo therapeutic evaluation of 6L3-1F3P11hR against SARS-CoV-2. K18-hACE2 mice (n = 5 per group) were intranasally challenged with 4 × 103 plaque-forming units of SARS-CoV-2 Omicron BA.2 at day 0. 6L3-1F3P11hR (3 mg/kg per dose) was administered via the intranasal route. Control groups included solvent-treated mice and nirmatrelvir-treated mice (100 mg/kg per dose, intragastric administration) as negative and positive controls, respectively. Both the control and experimental groups received the drug at the same time points with equal frequency. The animal experimental scheme figure was created in BioRender. L, R. (2026) https://BioRender.com/28q57t5. b SARS-CoV-2 RNA load was determined by qRT-PCR assay, normalized with β-actin. Quantitation of virus titer was done by plaque assays. To enable statistical analysis, values under LOD were assigned 0.0001 for qRT-PCR and 100 for plaque assay, respectively. Five animals were used per group (n = 5). Data are presented as mean ± SD. One-way ANOVA was used to compare the groups with the solvent-treated control. **P < 0.01, ***P < 0.001 and ****P < 0.0001. c Histopathology scores of the different treatment groups of mice. Five animals were used per group (n = 5). Data are presented as mean ± SD. One-way ANOVA was used to compare the groups with the solvent-treated control. *P < 0.1 and ***P < 0.001. d Representative images of hematoxylin and eosin-stained mouse lung sections at 4 dpi. The lung sections of the solvent-treated control mice showed prominent alveolar inflammation and congestion (asterisk), alveolar hemorrhage (black triangle), bronchiole luminal cell debris (black double-headed arrow), endothelium infiltrates (black arrows), perivascular or peribronchiolar infiltrates (blue arrows), and abundant viral nucleocapsid antigen (green) expression. In contrast, the lungs of mice treated with nirmatrelvir and the peptide, both prophylactically and therapeutically, demonstrated much alleviated histopathological changes and scarce viral nucleocapsid antigen expression. The nuclei were stained with 4′,6-diamidino-2-phenylindole (DAPI). Shown are representative images randomly selected from a pool of images for each group (n = 5 mice/group).
