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Cosalane halts HIV infection.

In the ongoing search for chemicals that inhibit HIV, the AIDS-causing virus, a medicinal chemist reports a novel, promising compound.

The new chemical, cosalane, stops HIV from infecting human immune cells grown in the laboratory, reports Mark S. Cushman, a medicinal chemist at Purdue University. Cosalane halts HIV infection by preventing an HIV surface protein called gp 120 from attaching to a membrane receptor on white blood cells, Cushman says.

Infection occurs when HIV attaches to and fuses with these cells, inserts its genetic material, and then replicates itself. That's where cosalane intervenes: Once the virus starts to bind to an immune cell, cosalane inhibits the "binding and postbinding fusion events," Cushman explains. Cosalane is a derivative of aurintricarboxylic acid (ATA), a chemical once used in the Swiss dye industry. Chemists found ATA effective at stopping the AIDS virus in the test tube, but it was too toxic for an AIDS treatment. Thus Cushman and his colleagues sought variations of ATA with fewer harmful side effects.

Cosalane has proved the most potent and least toxic of more than 70 ATA-like compounds tested so far, Cushman says. It is "active against a variety of HIV-1 strains and HIV-2, including strains that have proven themselves resistant to AZT [zidovudine] and other reverse transcriptase inhibitors." And cosalane shows little toxicity to noninfected cells, a potential improvement over drugs now used to treat HIV infection.

In addition, new drug-resistant strains of HIV have hampered AIDS treatment, Cushman says. But since cosalane uses a mechanism of action different from that of zidovudine and has proved toxic to some of those strains, Cushman believes this new compound may lead eventually to better AIDS drugs.

Cushman and researchers at the National Cancer Institute in Bethesda, Md., are now trying to produce large quantities of cosalane for preclinical testing. If all goes well, he says, studies in humans may begin within a year.
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Title Annotation:new compound inhibits HIV from infecting human immune cells in the laboratory
Author:Lipkin, Richard
Publication:Science News
Article Type:Brief Article
Date:Sep 4, 1993
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