To mount a successful attack, it sometimes helps to get a detailed look at the target. Now AIDS researchers have a fine-grained picture of a potential quarry: an HIV coat protein that helps the virus fuse with host cells. A crystal structure of a key portion of the protein, described in today's issue of Cell, suggests yet another target for people developing anti-HIV drugs.
Researchers have long known that HIV relies on its surface protein, gp41, to fuse with and infect cells. But they did not know the precise regions of gp41 responsible for fusion to occur. Peter Kim, David Chan, and colleagues at the Massachusetts Institute of Technology's Whitehead Institute for Biomedical Research in Cambridge crystallized the core of gp41 and used x-rays to map its structure. The team reports that the core has a "striking similarity" to a part of the flu virus that allows it to infect cells.
The Whitehead group calls gp41's core structures "a particularly attractive starting point" for drug designers. "Knowing [these] structures allows us to think of ways that we can inhibit fusion," says Chan. Joseph Sodroski, an AIDS researcher at the Dana-Farber Cancer Institute in Boston who specializes in HIV entry, says the new study is "a great confirmation" of what the Whitehead group has been working on. But there are at least a dozen other targets for which no anti-HIV drugs yet exist, and Sodroski cautions that this finding, too, will take years to apply. "As good as the molecular information is, we're still not at a point with rationale design that we can just make a drug," says Sodroski. "It's still very much a futuristic thing."