Treatment of lethal Pichinde virus infections in weanling LVG/Lak hamsters with ribavirin, ribamidine, selenazofurin, and ampligen.
A lethal Pichinde (An 4763 strain) virus infection was produced in 3-week-old random-bred Golden Syrian (LVG/Lak strain) hamsters inoculated intraperitoneally with virus, causing mortality in 6-9 days. High virus titers (> or = 10(7.5) cell culture infectious doses/g) were present in visceral organs, serum, brain and salivary glands near the time of death. Intraperitoneal treatments with ribavirin (10 and 32 mg/kg) and ribamidine (32, 100, and 320 mg/kg) for 10 days starting 24 h after virus challenge significantly decreased mortality and reduced virus titers by 100- to > 10,000-fold in liver, spleen, brain, and serum. Serum alanine aminotransferase (an indicator of liver damage) was also reduced in animals treated with the two compounds (ribavirin at 32 mg/kg; ribamidine at 100 and 320 mg/kg). Intraperitoneal selenazofurin (1-100 mg/kg per day for 10 days) and ampligen (0.5 and 5 mg/kg every other day for 5 injections) treatments provided neither protection from the lethal infection nor increased mean survival times. In fact, selenazofurin was overtly toxic, causing death of uninfected hamsters at 32 and 100 mg/kg. The random-bred LVG/Lak hamster appears to be a viable and cost-effective model for evaluating new therapies for arenavirus infections.
Antiviral Program, Utah State University, Logan 84322.
D F
DF
Smee
J
J
Gilbert
J A
JA
Leonhardt
B B
BB
Barnett
J H
JH
Huggins
R W
RW
Sidwell
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D006477:Arenaviruses, New World / Q000254:growth & development / Q000302:isolation & purification; D006224:Cricetinae; D005260:Female; D006478:Hemorrhagic Fever, American / Q000188:drug therapy*; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D011070:Poly I-C / Q000627:therapeutic use*; D011072:Poly U / Q000627:therapeutic use*; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D012263:Ribonucleosides / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms; D016019:Survival Analysis; D014018:Tissue Distribution; D014709:Vero Cells; D014886:Weaning
D000998:Antiviral Agents; D016566:Organoselenium Compounds; D012263:Ribonucleosides; D011072:Poly U; D012254:Ribavirin; C047490:poly(I).poly(c12,U); C039064:selenazofurin; D011070:Poly I-C; C026956:taribavirin