Fig. 7: Antiviral efficacy of Jun6504 in the EV-D68 infection mouse model.
From: A rationally designed 2C inhibitor prevents enterovirus D68-infected mice from developing paralysis
All control animals received vehicle alone (90% corn oil + 10% DMSO). All Jun6504 groups received 50 mg/kg of Jun6504 in the vehicle. All error bars represent SEM. a Paralysis scores are significantly lower in the Jun6504 group in the immediate treatment model (*p = 0.0004 Wilcoxon rank-sum; Control N = 10 [DPI14 = 5.35 ± 0.89], Jun6504 N = 10 [DPI14 = 0.40 ± 0.42]). b Weights from EV-D68-infected mice shown in Fig. a. Weight gain is also significantly increased by Jun6504 (*p = 0.003 t-test, Control DPI14 = 7.92 ± 0.46 g vs Jun6504 DPI14 = 9.29 ± 0.14 g). c Paralysis scores are significantly lower in Jun6504 group in 24-h delayed treatment model (*p = 0.0043 Wilcoxon rank-sum; Control N = 18 [DPI14 = 6.42 ± 0.63], Jun6504 N = 17 [DPI14 = 1.59 ± 0.61]). d Weights from the EV-D68-infected mice shown in Fig. c. Weight gain is also significantly increased by Jun6504 (*p = 0.0052 t-test; Control DPI14 = 8.65 ± 0.23 g vs Jun6504 DPI14 = 9.59 ± 0.27 g). e Pictorial representation of tissue harvest time points before treatment at DPI1 or after 4x daily injections on DPI5. The graph was created with Biorender.com. Li, K (2025) https://BioRender.com/kmwsykp. f Viral titer in muscle tissue from left quadriceps (infected muscle) prior to treatment (blue bar) and after 4 days of treatment (red and green bars). There is significantly more virus in the quadriceps muscle from untreated pups at DPI5 compared to Jun6504-treated pups (pooled t-test *p > 0.0001; Control N = 9 mean 119,544 ± 33,194TCID50 vs Jun6504 N = 9 mean 8762 ± 3080TCID50). The limit of detection in this assay is 1580TCID50. g Viral titer in spinal cords from the same animals shown in panel (f). There is significantly more virus in the spinal cord of untreated pups at DPI5 compared to Jun6504- treated pups (pooled t-test *p > 0.0484; Control mean 19,834 ± 11,519TCID50 vs Jun6504 mean 4520 ± 1796TCID50). All TCID50 values in untreated spinal cords from DPI1 are at the limit of detection. h Concentration of Jun6504 in spinal cords collected from uninfected pups. Jun6504 does enter the spinal cord (*p = 0.0151 Wilcoxon rank-sum, vehicle control N = 4 [50.0 ± 0.0] vs Jun6504 N = 5 [574.6 ± 100.5]). All vehicle control data is at the limit of detection. All statistics shown in Fig. 7 are two-sided (a–d, f–h). Source data are provided as a Source Data file.
