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Scientists discover new candidate drugs for treating HIV infection

Scientists have achieved a major step toward finding a new class of oral drugs to treat HIV infection. They have identified a class of compounds that prevent HIV infection by stopping the virus at its port of entry into the cell. Unlike currently used drugs that target HIV at other points during its life cycle--after it has already infected the cell--these compounds lock into a vulnerable "pocket" in the HIV's coat protein, preventing its fusion with cell membranes and thereby its ability to enter and infect cells.

The study is reported in this Friday's issue of Cell and was led by Dr. Peter S. Kim of the Whitehead Institute for Biomedical Research and the Howard Hughes Medical Institute.

To identify these compounds, the scientists first designed a fragment of HIV coat protein such that its vulnerable pocket was properly displayed. The pocket was first identified two years ago by the Kim lab as being a potential drug target. But until now, researchers had been unable to recreate the pocket in the laboratory. In this study, the scientists not only recreated the pocket but also identified compounds that bind to it, and showed that the binding of the compound to the pocket prevents HIV from infecting cells.

Their findings hold great promise for identifying a new class of oral drugs for HIV infection and AIDS.

"The compounds that we identified can serve as leads, or starting points, for the development of small-molecule drugs that stop HIV entry into cells," says Dr. Kim. "Alternately, scientists can use our 'pocket' to carry out high-throughput screening to identify other pocket-binding molecules. Finally, researchers can also identify new candidate drugs by their ability to disrupt the interaction between the pocket and the pocket-binding molecules."

To this end, and to speed up the process of finding new drugs, the Whitehead Institute will offer non-exclusive licenses of this technology to pharmaceutical and biotech companies worldw
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Contact: Seema Kumar
kumar@wi.mit.edu
617-258-6153
Whitehead Institute for Biomedical Research
1-Oct-1999


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