Fig. 6: In vivo antiviral efficacy of YL1004.

a,b 8- to 12-week-old female and male K18-hACE2 transgenic mice (n = 10) were intranasally challenged with 10000 PFU SARS-CoV-2 Omicron JN.1 strain. Mice in the treatment groups were orally treated with 100 mg/kg/dose YL1004 or Jun12682 twice per day. Control mice were treated with matching solvent only. Nasal turbinate and lung tissues were harvested at 3 dpi. for virological assessment by a RT-qPCR and b plaque assays. c,d 8- to 12-week-old female K18-hACE2 transgenic mice (n = 10) were intranasally challenged with 1250 PFU SARS-CoV-2 Delta strain. c Body weight and d survival of the infected mice were monitored for 14 days or until death of the animal. (e), Representative images of immunohistochemistry (IHC) staining which shows viral antigen expression (red) in the nasal turbinate and lung tissues of Omicron JN.1-infected mice (n = 3) at 3 dpi. f Representative images of haematoxylin-eosin (H&E) staining with the nasal turbinate and lung tissues of Omicron JN.1-infected mice (n = 3) at 3 dpi. Pathological findings were indicated as follows: inflammatory infiltrations (yellow dashed circle), alveolar collapse (cross) haemorrhage (asterisk), alveolar thickening (open arrowhead). Scale bar represents 200 µm and 100 µm under 10x and 20x magnification, respectively. Enlarged area was identified with dashed rectangle. Statistical significances were determined using Brown-Forsythe and Welch one-way ANOVA tests with Dunnett’s multiple comparisons test for P value adjustment in multiple comparisons (a,b), one-way ANOVA test (paired) with the Geisser-Greenhouse correction for sphericity (c) and log-rank (Mantel-Cox) tests (d). Each data point represents one biological repeat. Data represents mean ± SD from the indicated number of biological repeats. Data were obtained from three independent experiments. * represented P < 0.05 and ** represented P < 0.01. **** represented P < 0.0001. WT, wildtype SARS-CoV-2; Veh, vehicle.