Avian influenza H5N1
infections can cause severe, lethal human
infections. Whether influenza A virus treatments effectively ameliorate
avian influenza H5N1 human
infections is uncertain. The research objective was to evaluate the efficacy of novel
zinc and other metallo-ion formulations in two
influenza A mouse models. Mice infected with
influenza A/Duck/MN/1525/81 (H5N1) virus were treated orally 48 h before virus exposure and then twice daily for 13 days with
ZnAL42. The optimal dosing regimen for
ZnAL42 was achieved at 17.28 mg/kg 48 h prior to virus exposure, twice daily for 7 days. The survival rate was 80% compared with 10% in the untreated control group and a 100% survival rate with
ribavirin (75 mg/kg/day, twice a day for 5 days, beginning 4 h before virus exposure).
ZnAL42 treatment significantly lessened the decline in arterial oxygen saturation (SaO2; P < 0.001). This regimen was also well tolerated by the mice.
Manganese and
selenium formulations were not inhibitory to virus replication when given therapeutically. Mice were also infected with
influenza A/NWS/33 (H1N1) virus and were treated 48 h before virus exposure with three dosages of
ZnAL42 (8.64, 1.46 or 0.24 mg/kg/day). Treatment was by oral gavage twice daily for 13 days. The highest dose of
ZnAL42 was significantly inhibitory to the
virus infection as seen by prevention of deaths and lessening of decline in SaO2. The data suggest that the prophylactic use of
ZnAL42 is effective against
avian influenza H5N1 or H1N1 virus
infection in mice and should be further explored as an option for treating
human influenza virus infections.