A DRUG could soon be available that stops smallpox in its tracks. The pill has yet to be tested for safety, but is 100 times more potent than previous candidates for the job. It also destroys other viruses such as herpes.
Even before 11 September, bioterrorism experts were worried about our growing vulnerability to smallpox (快猫短视频, 3 November 2001, p 6). A single infected person could spark a worldwide outbreak, and the virus kills one in three of its victims. The US is now replenishing its stocks of the vaccine, which can save lives if given within four days of infection.
The trouble is that the vaccine has to be kept in a fridge and given by a nurse. The ideal anti-smallpox drug would be cheaper to produce and easier to distribute, and could be given at any stage of the disease. 鈥淭his new candidate has really moved us along toward that goal,鈥� says John Huggins of the US Army Medical Research Institute of Infectious Diseases, who鈥檚 been working on the new pill.
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The hunt began at the Centers for Disease Control and Prevention in Atlanta, Georgia, one of the two official repositories of smallpox stocks. Working in a maximum level biosafety suit, Huggins tested hundreds of antiviral drugs to see if they would stop the virus from reproducing in human cells.
One stood out: cidofovir, which is licensed to treat eye infections caused by cyto-megalovirus. But the drug has to be injected. That makes it no easier to give to patients than the existing smallpox vaccine. Nor is it readily taken up by cells. Which is where Karl Hostetler and James Beadle of the Veterans Affairs San Diego Healthcare System came in.
Their team has been improving cell absorption by linking drugs to a fatty chemical called phosphatidylcholine. 鈥淵our body absorbs a lot of it when you eat a hamburger,鈥� says Hostetler. When they tried it on cidofovir, the result was a huge boost in activity. The new drug, dubbed HDP-CDV, was 100 times more active than cidofovir against smallpox infections in human cells, the team told the 15th International Conference on Antiviral Research in Prague this week.
Huggins then tested the drug in mice infected with cowpox (as smallpox does not infect rodents). Animals given just a small dose of the drug once a day for 5 days were completely protected, whereas others died within nine days of infection. 鈥淪cale that up to a 70-kilogram person, and you鈥檇 get a pill the size of an aspirin,鈥� says Hostetler.
The next stage is to test the drug in primates, and see if it鈥檚 safe for people. All this work is going into a drug that everyone hopes will never have to be used for smallpox. But it could also be a valuable weapon against other viruses, including herpes, cytomegalovirus and Epstein-Barr.