Fig. 3: Efficacy of iHA-100 against lethal influenza virus infection in mice.

Five mice per group were intranasally inoculated with 5 MLD50 of A/whooper swan/Hokkaido/1/08 (H5N1) and were then intranasally administered iHA-100 (1.9 mg/kg/day) or zanamivir (3.3 mg/kg/day) at 0-4, 2-6, 4-8, or 6-10 dpi. Bodyweight and survival were monitored daily for 14 days. a Changes in body weight and b, survival rate. Results are shown as mean values, and error bars indicate SD. c–f Efficacy of early and delayed administration of iHA-100. H5N1-infected mice were administered iHA-100 (1.9 mg/kg/day) (closed squares) or vehicle (open triangles) at 0-4 dpi (c, e; early administration) or 4-8 dpi (d, f; delayed administration), and sacrificed at 3, 5, or 7 dpi (c, e; early administration), or 5, 7, or 9 dpi (d, f; delayed administration; 4 dpi sacrifice was performed before administration). Lung weights in iHA-100-treated mice (closed squares) or vehicle-treated mice (open triangles) with early (c) and delayed (d) administration were measured and normalized to the body weight. Virus titers in the lungs of mice with early (e) and delayed (f) administration were determined with plaque assays in MDCK cells (detection limit: 250 PFU/g lungs). Results are shown as mean values, and error bars indicate SD. g Effect of iHA-100 on H5N1-induced pathogenesis. Representative histopathologic findings with H&E staining of the lungs of infected mice given early administration (0-4 dpi) of vehicle or iHA-100 at 3 and 7 dpi are shown. Scale bar = 100 μm.