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Efficacy of the antipoxvirus compound ST-246 for treatment of severe orthopoxvirus infection.

Abstract
Efficacy of the new antipoxvirus compound ST-246 was evaluated as treatment of monkeypox (MPX) virus infection in a ground squirrel model of the disease. Ground squirrels were given a lethal dose of MPX virus and were then treated orally at various times post-inoculation (pi) with 100 mg/kg/day of ST-246. Morbidity and mortality, clinical laboratory results, viral load, and pathology of placebo and treatment groups were compared. All animals that started treatment with ST-246 on days 0, 1, 2, and 3 pi survived lethal challenge with MPX virus; 67% of animals treated on day 4 pi also survived. In contrast, 100% of the placebo group died. Most of the ST-246-treated animals showed no evidence of clinical disease or alteration of baseline clinical laboratory values and had minimal histopathologic changes. These results suggest that ST-246 is a promising candidate for early treatment of severe orthopoxvirus infection.
AuthorsElena Sbrana, Robert Jordan, Dennis E Hruby, Rosa I Mateo, Shu-Yuan Xiao, Marina Siirin, Patrick C Newman, Amelia P A Travassos DA Rosa, Robert B Tesh
JournalThe American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 76 Issue 4 Pg. 768-73 (Apr 2007) ISSN: 0002-9637 [Print] United States
PMID17426185 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antiviral Agents
  • Benzamides
  • Indoles
  • Isoindoles
  • ST-246
Topics
  • Animal Diseases (drug therapy, virology)
  • Animals
  • Antiviral Agents (pharmacokinetics, therapeutic use)
  • Benzamides (pharmacokinetics, therapeutic use)
  • Drug Administration Schedule
  • Indoles (pharmacokinetics, therapeutic use)
  • Isoindoles
  • Liver (pathology)
  • Lung (pathology)
  • Models, Animal
  • Monkeypox (drug therapy, mortality, veterinary, virology)
  • Sciuridae (virology)
  • Spleen (pathology)
  • Time Factors

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