Figure 2

Intraperitoneal injection of Sinococuline is more effective than its oral feeding in protecting the severely DENV infected AG129 mouse model. The in vitro made IC of mouse-adapted DENV-2 S221 strain and 4G2 mAb was inoculated in AG129 mice to establish the severe DENV infection, as reported previously²⁹ and Sinococuline was administered through the indicated route for evaluation of its efficacy as shown in pictorial diagram (a). The IC inoculated AG129 mice (n = 9) were either fed orally (four-times a day; QID; blue coloured curve with filled blue square) or intraperitoneally injected (two-times a day; BID, blue curve with empty blue square) with 10 mg/kg/day Sinococuline (made in sterile 1x PBS) for 5 days. All the mice were scored for their survival (b), morbidity (c), and body weight change (d) for 15 days post-infection. The only Sinococuline group was not infected with IC but fed orally with 10 mg/kg/day (QID; black curve with filled black square), considered as uninfected group. However, V: virus control mice group (green curve with filled green circle, infected with sublethal dose of DENV-2 S221, 2.0 × 10⁴ FIU/mouse) and IC group (grey curve with filled grey triangle, infected with IC) were not treated with Sinococuline and instead fed with only sterile 1× PBS (vehicle/placebo) orally (QID) for 5 days, and scored their survival, morbidity and body weight change for 15 days, similarly. The survival data (panel ‘b’) were analysed by Mantel–Cox test for significant difference in their survival rates, ns not significant, **statistically significant (p = 0.0010). On day 4 post-infection, a subset of mice from each group (n = 3) was euthanised, perfused with 1× PBS and their small intestinal lumens were flushed again with PBS and vascular leak was visualised qualitatively (e). In panel (e), small intestine of only one mouse from each group is represented here.