FIG. 2.

Viral titers in the lungs of infected mice treated with zanamivir or CS-8958 7 days before influenza virus infection. Mice were intranasally administered zanamivir at 4.8 μmol/kg (closed squares), 14 μmol/kg (closed circles), or 43 μmol/kg (closed triangles) (a); CS-8958 at 0.18 μmol/kg (closed squares), 0.53 μmol/kg (closed circles), or 1.6 μmol/kg (closed triangles) (b); or saline (open circles; a and b) 7 days before infection with influenza A virus (A/PR/8/34, 500 PFU). The viral titers (log₁₀ PFU/lungs) in the mouse lungs on days 1, 2, 3, and 4 are shown. Zanamivir doses of 4.8, 14, and 43 μmol/kg correspond to 1.6, 4.7, and 14 mg/kg, respectively; and CS-8958 doses of 0.18, 0.53, and 1.6 μmol/kg correspond to 0.085, 0.25, and 0.76 mg/kg, respectively. Each plot represents the mean ± standard deviation (n = 3). (Inset) AUCs (in percent) for zanamivir (closed circles) and CS-8958 (open circles) are plotted against the dose. The quantitative differences between the compounds were estimated to be 32.8 (P = 0.0028) by the parallel-line assay (ANCOVA).