AAC Accepts, published online ahead of print on 15 December 2008

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Antimicrob. Agents Chemother. doi:10.1128/AAC.01044-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

ST246 in vitro efficacy against smallpox and monkeypox

Scott K. Smith, Victoria A. Olson, Kevin L. Karem, Robert Jordan, Dennis E. Hruby, and Inger K. Damon^*

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; SIGA Technologies, Inc., Corvalis, Oregon

^* To whom correspondence should be addressed. Email: iad7{at}cdc.gov.

Since the eradication of smallpox (5) and the cessation of routine childhood vaccination for smallpox, the proportion of the world's population susceptible to infection with orthopoxviruses, such as variola (causative agent of smallpox) and monkeypox, has grown substantially. In the U.S. 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 6 variola and 7 monkeypox virus strains. We performed multiple assays to monitor cytopathic effect and to evaluate reduction of viral progeny production and release in the presence of the compound. ST-246 had a 50% effective concentration of 0.067 µM against variola and <0.04 µM against monkeypox. In a dose dependent manner, plaque size and comet tail formation were markedly reduced in the presence of the drug at low, non-cytotoxic concentrations between 0.015 and 0.05 µM. Our in vitro phenotype data suggest ST-246 similarly inhibits variola and monkeypox viruses by reducing the production/release of enveloped orthopoxvirus and support development of ST-246 as an antiviral therapeutic for severe systemic orthopoxvirus infections.

This article has been cited by other articles:

• Berhanu, A., King, D. S., Mosier, S., Jordan, R., Jones, K. F., Hruby, D. E., Grosenbach, D. W. (2009). ST-246 Inhibits In Vivo Poxvirus Dissemination, Virus Shedding, and Systemic Disease Manifestation. Antimicrob. Agents Chemother. 53: 4999-5009 [Abstract] [Full Text]