Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Reuters NewMedia - Thursday September 30, 1999
Gene Emery

Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute researchers said the weak link -- a pocket on the surface of the HIV virus -- could provide for the rapid screening of new oral anti-AIDS drugs that could be effective against all strains of the virus.

Dr. Peter Kim of the Whitehead Institute described the weak spot in the virus as a cavity on its surface that remains hidden until the human immunodeficiency virus attempts to latch onto a healthy cell. Only during the infection process does the virus unfold in a way that exposes the cavity, he said.

It is at that point that the virus is vulnerable, Kim said. A drug that wedges itself in the cavity should disable the virus. And once a drug has lodged itself inside, the virus "can't spit it out," Kim explained in an interview with Reuters.

"The virus becomes inactivated," unable to infect normal cells and the disruption "looks permanent," he added.

Kim and his colleagues have known about the cavity for two years, but have had difficulty duplicating it because the pocket is only exposed when it tries to infect a cell.

Once Kim and his colleagues were able to reproduce the cavity in the laboratory, he said, researchers were able to quickly identify several chemicals that seemed capable of becoming successful wedges.

Whitehead plans to offer nonexclusive licenses to experiment with the cavity in the hope that pharmaceutical and biotechnology companies with large libraries of chemicals will be able to find one that effectively clogs the pocket, potentially providing a new type of AIDS drug.

"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," Kim said.

It is important that the molecules be small because such drugs are the type that can be taken in pill form, which is far more convenient than the intravenous administration often required for treatments consisting of larger chemicals. Because "all of the strains (of HIV) we know of have the cavity," once an effective drug is found, it's not likely that HIV will be able to develop a resistance to it, Kim said.

And because the molecules that fit into the cavity would be twisted in a way that is uncommon to most living things, the drugs that clog it are unlikely to cause side effects or spark an unwanted reaction by the body's immune system, he said.

Existing HIV treatments are designed to attack the virus after it has infected healthy cells.
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