Influenza virus-inhibitory effects of intraperitoneally and aerosol-administered SP-303, a plant flavonoid.
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.
Sidwell
R W
RW
Institute for Antiviral Research, Utah State University, Logan 84322-5600.
Huffman
J H
JH
Moscon
B J
BJ
Warren
R P
RP
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001704:Biopolymers / Q000494:pharmacology / Q000627:therapeutic use*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D009980:Influenza A virus / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D013047:Specific Pathogen-Free Organisms; D044945:Proanthocyanidins
D000336:Aerosols; D000998:Antiviral Agents; D001704:Biopolymers; D002392:Catechin; C546704:crofelemer; D044945:Proanthocyanidins