NEW YORK (Reuters Health) - Adefovir (Hepsera), a drug used to treat chronic hepatitis B, is able to selectively inhibit the adenylyl cyclase activity of anthrax edema factor, new research shows. The drug binds to the factor’s catalytic site with greater affinity than does its own endogenous substrate, ATP.
In addition to the edema factor, Bacillus anthracis produces a toxin called lethal factor. Although much of the toxicity is mediated through the lethal factor, results from animal studies have suggested that blocking just the edema factor may still improve survival.
“For the first time, we have a clinically approved drug that, at least in tissue culture, completely eradicates...(edema factor), and does it at non-toxic doses,” senior author Dr. Wei-Jen Tang, from the University of Chicago, said in a statement.
The discovery that adefovir is active against an anthrax toxin came after Dr. Tang’s lab published a paper in January 2002 showing the 3-D structure of edema factor (see Reuters Health report January 23, 2002). A researcher working with adefovir apparently saw the news coverage and, thinking that adefovir might have some activity against the factor, proceeded to send the drug to Dr. Tang’s lab for testing.
As reported in the February 16th online edition of the Proceedings of the National Academy of Sciences, Dr. Tang’s found that by blocking the factor’s adenylyl cyclase activity, adefovir effectively inhibits the cAMP accumulation that typically occurs.
The researchers found that the drug inhibits the adenylyl cyclase activity with high affinity.
“Our studies suggest that (adefovir) may be a promising adjunctive therapy against anthrax and other human diseases caused by pathogenic bacteria that secrete adenylyl cyclase toxins, such Bordetella pertussis, Pseudomonas aeruginosa, and Yersinia pestis,” the investigators conclude.
Source: Proc Natl Acad Sci USA 2004. [ Google search on this article ]
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