Fig. 7. The CLK2 inhibitor TG003 exerts effects in vitro and in vivo.

A THP-1 cells were infected with VSV-GFP at an MOI of 1 for 12 h in the presence or absence of TG003 (20 µM) before phase contrast and fluorescence microscopy and flow cytometric analysis. The scale bar is 250 µm. B THP-1 cells were infected with VSV-GFP at an MOI of 1 for 1 h in the presence or absence of TG003 (20 µM) before the medium was replaced, and the cells were cultured for 24 h. Then, the supernatants were diluted and added to Vero cells for plaque assays (n = 3). C Real-time PCR analysis of IFNB1 and RANTES mRNA levels in the presence or absence of TG003 in THP-1 cells infected with SeV for 12 h (n = 3). D TG003 alleviated VSV-induced conjunctivitis at 10 mg/kg or 20 mg/kg. E–G The effects of TG003 on the antiviral response in vivo. 6-week-old female mice (n = 6) were infected with VSV (2 × 10⁷ pfu/g), after which DMSO or 10 mg/kg or 20 mg/kg TG003 was intraperitoneally injected three times each day. E Mouse survival (Kaplan‒Meier curve) was monitored for 15 days. F Serum samples were collected after 24 h and subjected to plaque assays (n = 6) and (G) ELISA analysis of Ifnb1 and Rantes (n = 5). H H&E staining and ear thickness in IMQ-treated mice on Day 6 (n = 6). I, J Real-time PCR analysis of Il-17a and Il-17f mRNA levels after treatment of Clk2-deficient mice with IMQ for 6 days or after intraperitoneal injection of TG003 (n = 6). The data are representative of three independent experiments. The data are presented as the means ± SEMs. Statistical significance was analyzed by two-tailed Student’s t test (B, F) or two-tailed ANOVA (C, G–J) (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001). Source data (A–J) are provided as a Source Data file.