Figure 6. In vivo validation of selected chemical inhibitors and proviral factors.

(a,b) Health status and body weight evolution in 9-day-old C57BL/6^clk1−/− or C57BL/6^clk1+/+ mice infected intradermally with CHIKV C21 (10⁴ PFU) and killed at the appearance of paralysis. (c) Experimental design of the intradermal infection of the young mouse model used for tivozanib. (d–f) Effect of daily tivozanib (tivo) treatment on C57BL/6 mouse survival, paralysis and body weight change in response to CHIKV C21 infection. (g) Health status of each mouse with paralysis, estimated by measuring the area under the body weight curve. (h) CHIKV viral load measured 3 days post infection in the indicated organs obtained from mice treated with tivozanib as in c (n=9 for all data sets). (i,j) Experimental design of the footpad infection of adult mice model used and viral titres measured in C57BL/6 mice treated with pimozide (pimo, per os, n=15 for both data sets) or TOFA (i.p., n=11 for both data sets) or the corresponding vehicles before infection with CHIKV C21 (10³ PFU). Data in b,f and g represented as the mean±s.e.m.; in h,i and j as the median±interquartile range; each dot represents one mouse. All data obtained from at least two independent experiments. Statistics were calculated using Log-rank (Mantel–Cox) test in a,d and e, two-sided t-test for two independent samples in g and Mann–Whitney test in h,i and j, (*P<0.05; ^NSP≥0.05). AUC, area under curve; d, days; i.p., intraperitoneal; NS, not significant.