Fig. 3: Antiviral efficacy of HNC-1664 treatment in K18-hACE2 transgenic mice.
a Schematic flow chart of the experimental design. K18-hACE2 transgenic mice were challenged with 1 × 105 PFU of the SARS-CoV-2 delta strain. Starting at 2 h post infection (h.p.i.), each mouse was administered HNC-1664 (n = 7), molnupiravir (n = 6) or vehicle (n = 6) by oral gavage twice daily. The image elements were created with BioRender. b Mouse survival was monitored daily until 4 days post infection (d.p.i.). The data are shown as Kaplan-Meier survival curves. c–e The number of infectious virus particles in the nasal turbinate (c), trachea (d) and lungs (e) of infected mice from the HNC-1664 (n = 7), molnupiravir (n = 6) and vehicle (n = 5) groups was determined via plaque assay. f–h The number of viral genes in the nasal turbinate (f), trachea (g) and lungs (h) of infected mice from the HNC-1664 (n = 7), molnupiravir (n = 6) and vehicle (n = 5) groups was determined via qRT-PCR. i, j HNC-1664 decreased damage in infected mouse lung tissue. Representative images of immunohistochemical staining (i) showing the presence of the SARS-CoV-2 NP protein (brown) in the lungs of infected mice at 4 d.p.i. Scale bar, 200 µm. Representative images of hematoxylin and eosin (H&E) staining (j) showing virus-induced damage in the lungs of infected mice at 4 d.p.i. Scale bar, 200 µm. The alveoli, bronchioles, and blood vessels of the lung were enlarged, and representative images are shown with enlarged images ①, ②, and ③, respectively. Scale bar, 50 µm. The data are presented as the mean ± SD (c–h). Statistical significance was assessed by one-way ANOVA with Dunnett’s post-hoc test compared with the vehicle control group. **P < 0.01, ***P < 0.001, ****P < 0.0001. LOD limit of detection.
