Effect of oral gavage treatment with ZnAL42 and other metallo-ion formulations on influenza A H5N1 and H1N1 virus infections in mice.
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.
Barnard
Dale L
DL
Institute for Antiviral Research, Utah State University, Logan, UT, USA. honery@usu.edu
Wong
Min-Hui
MH
Bailey
Kevin
K
Day
Craig W
CW
Sidwell
Robert W
RW
Hickok
Stephen S
SS
Hall
Tony J
TJ
D000284:Administration, Oral; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects*; D008345:Manganese / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000517:prevention & control*; D010100:Oxygen / Q000097:blood; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology; D012643:Selenium / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D016019:Survival Analysis; D017967:Zinc Compounds / Q000494:pharmacology*
D017607:Aluminum Compounds; D000998:Antiviral Agents; D017967:Zinc Compounds; C522745:ZnAL42; D008345:Manganese; D012254:Ribavirin; D012643:Selenium; D010100:Oxygen