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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.
Received July 13, 2006. Accepted for publication December 31, 2006.
Acknowledgments: We thank Hilda Guzman for technical assistance and Dora Salinas for assistance in preparing the manuscript.
Financial support: This study was supported by contract NO1-AI25489 and grant U54-AI57156 from the National Institutes of Health. Rosa I. Mateo was supported by a postdoctoral fellowship from the James W. McLaughlin Foundation, University of Texas Medical Branch.
Disclosure: Robert Jordan and Dennis E. Hruby are employees of SIGA Technologies, Inc., the company that produced ST-246. This statement is made in the interest of full disclosure and not because the authors consider this to be a conflict of interest.
* Address correspondence to Robert B. Tesh, Department of Pathology University of Texas Medical Branch 301 University Boulevard, Galveston, TX 77555-0609. E-mail: rtesh{at}utmb.edu
Authors’ addresses: Elena Sbrana, Rosa I. Mateo, Shu-Yuan Xiao, Marina Siirin, Patrick C. Newman, Amelia P. A. Travassos da Rosa, and Robert B. Tesh. Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0609, Telephone: 409-747-2431, Fax: 409-747-2429. Robert Jordan and Dennis E. Hruby, SIGA Technologies, Inc., 4575 SW Research Way, Suite 230, Corvallis, OR 97333, Telephone: 541-753-2000, Fax: 541-753-9999.
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