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Antimicrobial Agents and Chemotherapy, March 2009, p. 1007-1012, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.01044-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

In Vitro Efficacy of ST246 against Smallpox and Monkeypox{triangledown}

Scott K. Smith,1 Victoria A. Olson,1 Kevin L. Karem,1 Robert Jordan,2 Dennis E. Hruby,2 and Inger K. Damon1*

Poxvirus Team, Poxvirus and Rabies Branch, Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Viral, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia,1 SIGA Technologies, Inc., Corvallis, Oregon2

Received 4 August 2008/ Returned for modification 19 September 2008/ Accepted 24 November 2008

Since the eradication of smallpox and the cessation of routine childhood vaccination for smallpox, the proportion of the world's population susceptible to infection with orthopoxviruses, such as variola virus (the causative agent of smallpox) and monkeypox virus, has grown substantially. In the United States, the only vaccines for smallpox licensed by the Food and Drug Administration (FDA) have been live virus vaccines. Unfortunately, a substantial number of people cannot receive live virus vaccines due to contraindications. Furthermore, no antiviral drugs have been fully approved by the FDA for the prevention or treatment of orthopoxvirus infection. Here, we show the inhibitory effect of one new antiviral compound, ST-246, on the in vitro growth properties of six variola virus strains and seven monkeypox virus strains. We performed multiple assays to monitor the cytopathic effect and to evaluate the reduction of viral progeny production and release in the presence of the compound. ST-246 had 50% effective concentrations of ≤0.067 µM against variola virus and <0.04 µM against monkeypox virus. In a dose-dependent manner, plaque size and comet tail formation were markedly reduced in the presence of the drug at low, noncytotoxic concentrations between 0.015 and 0.05 µM. Our in vitro phenotype data suggest that ST-246 inhibits variola and monkeypox viruses similarly by reducing the production and release of enveloped orthopoxvirus and support the development of ST-246 as an antiviral therapeutic compound for the treatment of severe systemic orthopoxvirus infections.

* Corresponding author. Mailing address: Centers for Disease Control and Prevention, Mail Stop G-06, 1600 Clifton Road, NE, Atlanta, GA 30333. Phone: (404) 639-4931. Fax: (404) 639-1060. E-mail: iad7{at}cdc.gov

{triangledown} Published ahead of print on 15 December 2008.

Antimicrobial Agents and Chemotherapy, March 2009, p. 1007-1012, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.01044-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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