Prophylactic and therapeutic activities of 7-thia-8-oxoguanosine against Punta Toro virus infections in mice.
The biological response modifier 7-thia-8-oxoguanosine was evaluated in mice against the hepatotropic Adames strain of Punta Toro virus. When administered intraperitoneally in divided doses, significant protection from death was conferred at doses of 50 and 100 mg/kg/day given 24 and 17 h pre-virus inoculation, 25-100 mg/kg/day administered 4 h pre- and 3 h post-virus challenge, and 12.5 to 100 mg/kg/day administered 24 and 31 h after virus inoculation. These doses preventing death reduced liver icterus scores, serum alanine aminotransferase and aspartate aminotransferase levels, and liver and serum virus titers relative to placebo controls. Full daily doses administered at 24 h were somewhat less protective to mice than divided daily doses starting at the same time. The initiation of treatment could be delayed as late as 36 h after virus inoculation, resulting in complete protection from mortality at 100 mg/kg/day. This prevention of death occurred despite the acute nature of the infection which resulted in deaths by 96 h in the placebo-treated controls. These results show that 7-thia-8-oxoguanosine has both prophylactic and therapeutic potential as an anti-Phlebovirus agent. Interferon induction appears to be the reason for antiviral activity in this model, since up to 10,000 units of interferon/ml were induced in mice 1 h after treatment with 100 mg 7-thia-8-oxoguanosine per kg, and antibody to interferon alpha/beta administered shortly after treatment with the nucleoside negated the antiviral effect.
Smee
D F
DF
Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan 84322-5600.
Huffman
J H
JH
Gessaman
A C
AC
Huggins
J W
JW
Sidwell
R W
RW
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D002044:Bunyaviridae Infections / Q000188:drug therapy* / Q000517:prevention & control; D004334:Drug Administration Schedule; D005260:Female; D006151:Guanosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D007274:Injections, Intraperitoneal; D007372:Interferons / Q000096:biosynthesis; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D013047:Specific Pathogen-Free Organisms
D000998:Antiviral Agents; D006151:Guanosine; C061136:isatoribine; D007372:Interferons; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase