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Molecules inhibit HIV protease, could lead to new line of attack against AIDS

Researchers have identified a molecule with the ability to inhibit a key enzyme of HIV, a finding that could limit the spread of the virus that causes AIDS. The laboratory test results are reported in the February 7 issue of the Journal of the American Chemical Society, a peer-reviewed journal of the American Chemical Society, the world's largest scientific society.

Known as polyoxometalate, or POM, the molecule stopped HIV protease at a molecular location away from its "active site," according to Craig Hill, an author of the paper and chemistry professor at Emory University in Atlanta. The preliminary research is the first report of such inhibition, which Hill believes could - in combination with conventional HIV drugs - reduce the chances of spreading the virus, particularly drug-resistant strains.

HIV protease forms proteins at its active site that can lead to the virus. The virus can then replicate itself throughout the body. The POM molecule provides a "second line of attack" against HIV away from the active site, Hill noted. Preventing protease activity is not a cure for HIV, but could help manage the virus's spread and delay the onset of full-blown AIDS.

Since HIV can become resistant to existing drugs, the POM molecule would likely function as a complementary treatment along with known protease inhibitors and reverse transcriptase inhibitors like AZT, Hill said.

"Basically it's really interesting scientifically, but we're not quite sure what it means to patients with HIV just yet," Hill said. "This work documents, in a very concrete way, a new mode of inhibition of the HIV protease by a small molecule."

The POM family includes more than 10,000 molecules. Some have been used commercially as catalysts and others possess known antiviral activities. The researchers were surprised to discover that the POM molecule inhibited protease, Hill said. The finding defies conventional wisdom that effective drugs must bind at the enzyme's active sit
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Contact: Beverly Hassell
b_hassell@acs.org
202-872-4065
American Chemical Society
23-Jan-2001


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