Amidst elevated concerns about the possibility of a biological attack involving smallpox after the terrorist events of last fall, the search for drugs to combat the dread infection has intensified. To that end, findings announced today at the 15th International Conference on Antiviral Research in Prague may represent an important advance. Researchers reported that an oral drug known as hexadecyloxypropyl-cidofovir (HDP-CDV) stymies smallpox and its kin in tissue culture and in mice.

Routine smallpox vaccination ended in 1972, and the variola virus that causes smallpox was declared eradicated several years later. Laboratories in the U.S and in Russia hold the last official samples of the virus, but experts have feared for some time that terrorists may have samples of their own. Although the U.S. has a supply of the vaccine remaining, serious adverse reactions to it can occur. Researchers have thus been searching for alternatives.

The new drug appears especially promising. In addition to blocking the replication of several strains of smallpox in tissue culture, HDP-CDV also effectively combated the closely related cowpox virus in mice. A derivative of the compound cidofovir (which has been shown to be effective against smallpox in animals), HDP-CDV is both more potent and more easily administered than its predecessor, report Karl Y. Hostetler of the University of California, San Diego, and colleagues. "[Cidofovir] can only be given intravenously," Hostetler explains. "If you've got thousands of people exposed to smallpox, a drug that needs to be injected would be difficult to use widely." HDP-CDV, in contrast, could potentially be given in pill form over a period of five to 14 days for the prevention and treatment of smallpox.

"Until now, the eradication and control of smallpox relied upon vaccination," Hostetler observes. But the new results "suggest that antiviral drugs given orally in a regimen consisting of as few as five doses might be used an alternative to treat and contain a future outbreak of smallpox, especially in those individuals who cannot safely be vaccinated." Additional testing of HDP-CDV in animals will be required before human trials can begin, however.

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