Fig. 8: Antiviral efficacy of C10 in a K18-hACE2 transgenic mouse model. | Nature Communications

Fig. 8: Antiviral efficacy of C10 in a K18-hACE2 transgenic mouse model.

From: SARS-CoV-2 NSP14 inhibitor exhibits potent antiviral activity and reverses NSP14-driven host modulation

Fig. 8: Antiviral efficacy of C10 in a K18-hACE2 transgenic mouse model.

a Plasma drug concentrations of C7 and C10 in male ICR mice (6-8 weeks) following intraperitoneal injection (i.p.) of 50 mg/kg (C7) and 70 mg/kg (C10) in a 5% dimethyl sulfoxide and 95% cyclodextrin solution (cyclodextrin: saline mass ratio = 1:2) (n = 3 per group). Data are presented as mean ± SD from three independent replicates. b In vitro pharmacokinetic (PK) parameters of C7 and C10. Data are presented as mean ± SD from three independent replicates. AUC, Area Under the Curve. c, d Body weight loss (c) and survival rate (d) in uninfected mice following administration of C10 or vehicle (twice daily, B.I.D.). Body weight data are presented as mean ± SD from three independent replicates. e Experimental design for the study of 3-day treatment study. K18-ACE2 mice were intranasally (i.n.) inoculated with 5000 PFU of SARS-CoV-2 strain (Wuhan-Hu-1), followed by intraperitoneal injection of 60 mg/kg, 120 mg/kg, or 180 mg/kg C10, 15 mg/kg remdesivir, or vehicle B.I.D for 3 days. Created in BioRender. Che, J. (2025) https://BioRender.com/r92e290. f SARS-CoV−2 lung viral titers at day 4 post-infection (DPI). Titers are expressed as log10(PFU/g) of lung tissue. Data are shown as mean ± SD. Sample sizes: n = 5 (vehicle), n = 4 (C10 60 and 120 mg/kg), n = 3 (remdesivir 15 mg/kg). Statistical significance was analyzed calculated by two-sided unpaired t-test. g Representative haematoxylin and eosin (H&E)-stained lung sections at 4 DPI from vehicle-, 120 mg/kg C10-, and 15 mg/kg remdesivir-treated mice. Histological features include alveolar wall thickening (blue arrow), capillary congestion (red arrow), and alveolar dilation (green arrow). Scale bars, 100 μm. Three times experiments were repeated independently with similar results. h Immunohistochemical staining of SARS-CoV−2 nucleocapsid protein (brown) in lung sections at 4 DPI from vehicle-, C10-, and remdesivir-treated mice. Scale bars, 100 μm. Three times experiments were repeated independently with similar results. i, j Summary scores of lung lesions (i) and of nucleocapsid immunostaining of lungs (j). Data are shown as mean ± SD (n  =  5). Statistical significance was analyzed by two-sided unpaired t-test. Source data are provided as a Source Data file.

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