Fig. 2: The in vivo antiviral efficacy of prophylactic and therapeutic TMP1 treatment against SARS-CoV-2 infection.
From: An orally available Mpro/TMPRSS2 bispecific inhibitor with potent anti-coronavirus efficacy in vivo
a Pharmacokinetics of TMP1, Paxlovid and camostat oral delivery in mice (n = 3). b Schematic illustration of SARS-CoV-2 infection in K18-hACE2 transgenic mice with therapeutic or prophylactic TMP1 treatment (Created in BioRender)104. c Quantification of sgE gene of SARS-CoV-2 in the nasal turbinate and lung tissues of the infected mice (n = 6) with prophylactic treatment. d Quantification of the infectious viral titres in the nasal turbinate and lung tissues of the infected mice (n = 6) with prophylactic treatment. e Viral N protein expression in the nasal turbinate and lung tissues of infected mice (n = 3) with prophylactic treatment was quantified with ImageJ. f Representative images of SARS-CoV-2 N protein expression (black arrow) in nasal turbinate and lung tissue of the infected mice. Scale bar represents 100 µm. g Histology analysis of the nasal turbinate and lung tissue of the infected mice by H&E staining. Scale bar represents 100 µm. Black arrowhead, nasal epithelial desquamation; open arrowhead, alveolar collapse; dashed circle, inflammation infiltrations in alveolar septa; asterisk, bronchiolar epithelium damage. h Body weight change of the female (n = 6) and male (n = 11 and 13 for vehicle and TMP1 group, respectively) infected mice with or without TMP1 prophylactic treatment. i Survival of the female (n = 6) and male (n = 11 and 13 for vehicle and TMP1 group, respectively) infected mice with or without TMP1 prophylactic treatment. j Quantification of sgE gene of SARS-CoV-2 in the nasal turbinate and lung tissues of the infected mice (n = 10) with delayed therapeutic treatment. Each data point represents one biological repeat. Data represents mean ± SEM from the indicated number of biological repeats. Statistical significances were determined using one way-ANOVA with Dunnett’s multiple comparisons test (c–e), (j) and log-rank (Mantel-Cox) tests (i). Data were obtained from three independent experiments. * represented p < 0.05 and ** represented p < 0.01. *** represented p < 0.001, **** represented p < 0.0001. WT wildtype SARS-CoV-2, Veh vehicle, PAX Paxlovid.
