Fig. 2: In vivo efficacy of JNJ-1802 (b.i.d.) against DENV-1–4 after infection in AG129 mice.
From: Blocking NS3–NS4B interaction inhibits dengue virus in non-human primates
a, Schematic of viraemia studies against DENV-2. b, The effect of JNJ-1802 on viraemia on day 3 after infection in DENV-2-infected mice treated b.i.d. with 60, 20, 6, 2, 0.6, 0.2 mg per kg per day JNJ-1802 (n = 7, 14, 14, 16, 16 and 13, respectively; without anti-flavivirus antibodies), compared with vehicle-treated mice (n = 24). Treatment started 1 h before infection. Undetermined Ct values imputed at a value of 40 (the limit of detection (LOD)) correspond to 2.6 log10 viral RNA copies per ml. Pooled data of three independent studies were analysed using two-way ANOVA with Dunnett’s multiple-comparison test. The LLOQ is 3.7 log10 viral RNA copies per ml. c, Schematic of the survival study. d, The effect of JNJ-1802 on survival in mice treated with anti-flavivirus antibodies (clone 4G2) receiving b.i.d. 20, 6, 2, 0.6 or 0 mg per kg per day JNJ-1802 starting 1 h before infection. Data are from a single study (n = 10 mice per group). Two-sided Fisher’s exact tests were used on day 25 with Bonferroni’s multiple-comparison test. e, Outline of the viraemia/survival studies against DENV-1, DENV-3 and DENV-4. f–k, The effect of JNJ-1802 on survival (n = 10 mice per group, except for DENV-3 vehicle, for which n = 11 mice per group) (f–h) and viraemia (n = 5 mice per group) on day 3 after infection (i–k) in mice challenged with DENV-1/West Pac (f,i), DENV-3/C0360/94 (g,j) or DENV-4/703/4 (h,k), treated b.i.d. with 60, 6 or 0 mg per kg per day JNJ-1802. Treatment started 1 h before infection. The LOD is 1.7 log10 viral RNA copies per ml. Two-sided Fisher’s exact tests were used on day 6 (survival) with Bonferroni’s multiple-comparison test. For viraemia, ordinary one-way ANOVA with Dunnett’s multiple-comparison test (DENV-1) and Kruskal–Wallis tests with Dunn’s multiple-comparison test (DENV-3 and DENV-4) were performed. P values are shown in the figures. HEP, human end point. For a, c and e, the schematics were adapted from ref. 3. The dagger symbol indicates the day of euthanasia.
