1. Academic Validation
  2. Effects of four antiviral substances on lethal vaccinia virus (IHD strain) respiratory infections in mice

Effects of four antiviral substances on lethal vaccinia virus (IHD strain) respiratory infections in mice

  • Int J Antimicrob Agents. 2004 May;23(5):430-7. doi: 10.1016/j.ijantimicag.2003.10.010.
Donald F Smee 1 Min-Hui Wong Kevin W Bailey James R Beadle Karl Y Hostetler Robert W Sidwell
Affiliations

Affiliation

  • 1 Department of Animal, Dairy and Veterinary Sciences, Institute for Antiviral Research, Utah State University, Logan, UT 84322-5600, USA. [email protected]
Abstract

Intranasal Infection of BALB/c mice with the IHD strain of vaccinia virus was found to cause pneumonia, profound weight loss and death. Cidofovir, hexadecyloxypropyl-cidofovir (HDP-CDV), the diacetate ester prodrug of 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (HOE961), and ribavirin were used to treat the infections starting 24h after virus exposure. Single intraperitoneal (i.p.) cidofovir treatments of 100 and 30 mg/kg led to 90-100% survival compared with no survivors in the placebo group, whereas a 10 mg/kg dose was ineffective. The 100 mg/kg treatment reduced lung and snout virus titres on day 3 of the Infection by 20- and 8-fold, respectively. Mean arterial oxygen saturation levels in these two cidofovir treatment groups were significantly higher than placebo on days 4 through 6 of the Infection, indicating an improvement in lung function. Effects of cidofovir on viral pathogenesis were studied on days 1, 3 and 5 of the Infection, and demonstrated statistically significant reductions in lung consolidation scores, lung weights, lung virus titre and snout virus titres on days 3 and 5. Cidofovir treatment also reduced virus titres in other tissues and body fluid, including blood, brain, heart, liver, salivary gland and spleen. HDP-CDV was given by oral gavage at 100, 50 and 25mg/kg doses one time only, resulting in 80-100% survival. Lower daily oral doses of 10 and 5mg/kg per day given for 5 days protected only 30% of Animals from death. Oral doses (100, 50 and 25 mg/kg per day) of HOE961 for 5 days protected all Animals, whereas equivalent oral doses of ribavirin were completely ineffective. The rapidity of recovery from weight loss during the Infection was a function of dose of compound administered. These data indicate the utility of parenteral cidofovir, oral HDP-CDV and oral HOE961 in treating severe respiratory infections caused by this virus.

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