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Influenza virus-inhibitory effects of intraperitoneally and aerosol-administered SP-303, a plant flavonoid
R W Sidwell1, J H Huffman, B J Moscon
1Institute for Antiviral Research, Utah State University, Logan 84322-5600.
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.
Insights
The phenolic biopolymer SP-303 showed antiviral effects against influenza A (H1N1) in mice, reducing lung consolidation and increasing survival time, though high doses were toxic and aerosol delivery caused temporary hypothermia.
Area of Science:
- Virology
- Pharmacology
- Biochemistry
Background:
- Influenza A (H1N1) poses a significant global health threat.
- Development of novel antiviral therapies is crucial for pandemic preparedness.
- Phenolic biopolymers represent a potential class of therapeutic agents.
Purpose of the Study:
- To evaluate the efficacy of the phenolic biopolymer SP-303 against influenza A (H1N1) in a murine model.
- To assess the impact of different administration routes (intraperitoneal and aerosol) and schedules on SP-303's antiviral activity.
- To determine the toxicity and side effects associated with SP-303 treatment.
Main Methods:
- Experimentally induced influenza A (H1N1) infections in mice.
- Administration of SP-303 via intraperitoneal injection and small-particle aerosol (SPA).
- Evaluation of outcomes including lung consolidation, survival rates, lung virus titers, arterial oxygen saturation, and body temperature.
Main Results:
- Intraperitoneal SP-303 reduced lung consolidation and extended survival, but high doses were toxic.
- SPA administration showed antiviral effects, improving survival and reducing lung consolidation.
- SPA treatment did not inhibit lung virus titer but improved oxygen saturation; transient hypothermia was observed.
Conclusions:
- SP-303 demonstrates therapeutic potential against influenza A (H1N1) in mice, particularly when delivered via aerosol.
- Further research is needed to optimize dosage and administration for safety and efficacy.
- SP-303's effects on physiological parameters like oxygen saturation warrant further investigation.