Influenza Virus-Inhibitory Effects of Intraperitoneally and Aerosol-Administered SP-303, a Plant Flavonoid

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Abstract
The phenolic biopolymer SP-303 was evaluated against experimentally induced influenza A (H1N1) virus infections in mice in a series of experiments. When 30, 10 or 3 mg/kg/day of SP-303 were administered intraperitoneally once daily for 8 days beginning either 48 h before or 4 h after virus exposure, only lung consolidation was significantly reduced; extended (p < 0.01) mean day to death was also seen in the late-therapy groups. The high dosage was lethally toxic in this experiment. A small-particle aerosol (SPA) of 10, 5 and 2.5 mg/ml of SP-303, administered for 1 h three times daily for 5 days beginning 4 h after virus exposure, exerted a similar antiviral effect. Twice-daily 1-hour SPA treatments for 3 days beginning 24 h before virus exposure using 4.3 mg/ml of SP-303 resulted in significant increases in mean day to death and reductions of lung consolidation but no inhibition of lung virus titer. Declines in influenza-induced arterial oxygen saturation, as determined by pulse oximetry, were less in all animals treated with SP-303 by SPA, but this reduced decline was significant (p < 0.01) only in the last experiment. Mice receiving SP-303 by SPA exhibited consistent but reversible hypothermia immediately after termination of treatment.

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