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Researchers Uncover Potential New Smallpox Treatment By Chris Schneidmiller WASHINGTON — Researchers may have found a new route for blocking smallpox infection by targeting the cellular pathways the virus uses to replicate in a body, the National Institute of Allergy and Infectious Diseases announced this week (see GSN, Jan. 18). Existing antiviral drugs are used to block the growth of the virus itself. Tests found, however, that an experimental anticancer drug was able to inhibit the process by which the smallpox growth factor protein attaches to cells and prepares them to produce new virus particles, according to a research article published in the February issue of the Journal of Clinical Investigation. The smallpox vaccine can take weeks to provide immunity. There is one antiviral drug known to affect the virus, but it carries a potential side effect of kidney damage and could be overcome by a purposely engineered virus or the infection’s natural increase in resistance to the treatment, Mark Challberg, emerging viral diseases team leader at the National Institute of Allergy and Infectious Diseases, said in an interview. “It wouldn’t be the greatest drug in an emergency situation,” said Challberg, who co-authored a JCI commentary on the research. “For that reason there’s a need for drugs that would be easier to use.” The smallpox virus is unlikely to have time to develop resistance to a short-term drug treatment on unchanging cell chemical pathways. The drugs by necessity would be given for a limited time to ensure they do not damage cells, Challberg said. However, they could slow the infection while the body’s immune system — either naturally or through vaccinations — prepares to deal with the virus. The research was conducted with NIAID funding by scientists from the Dana-Farber Cancer Institute in Boston, the University of Massachusetts Medical School and the Centers for Disease Control and Prevention. “The threat of smallpox virus being used as a bioterror weapon makes it imperative that we pursue not only improved vaccines, but also novel therapeutic strategies such as this that could be employed quickly in the event of a deliberate release of the virus,” National Institutes of Health Director Elias Zerhouni said in the press release. Senior research author Ellis Reinherz of the Dana-Farber Cancer Institute began studying smallpox treatments following the Sept. 11, 2001, terrorism attacks, Challberg said. Reinherz could not be reached for comment. Scientists in this project tested the experimental drug against smallpox that had been introduced into monkey kidney cells and in live mice. Virus spread in the lab-grown kidney cells was “significantly impaired” when the experimental drug was used, the NIH press release states. The same drug, when used with a single dose of an anti-infection antibody, eliminated the virus from mice’s lungs within eight days of infection. Challberg estimated that it would take three to five years before this type of smallpox treatment could be ready for use. The drug used in this project could not fully inhibit the smallpox when high doses were given to mice. Researchers will look for similar medication that could provide stronger protection, Challberg said. Additional testing will also be necessary, he said.
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