U.'s peptide discovery spurs hope of HIV prevention and treatment

University of Utah School of Medicine researchers have discovered a potent peptide that may prevent HIV from entering human cells, sparking hope of both prevention and new treatment options.

The "D-peptide" is 40,000 times more potent at preventing HIV from entering human cells than other known agents of the same class of inhibitors, says Dr. Michael S. Kay, assistant professor of biochemistry and lead author of research published this week in the Proceedings of the National Academy of Sciences online.

At the heart of their findings are HIV's "pocket" and peptides, which are natural and artificial compounds including hormones and antibiotics that tackle various biological jobs. The researchers screened "billions" of peptides before they found a class called D-peptides, says Brett Welch, a U. graduate student and the study's first author.

The D-peptides bind tightly to HIV's "pocket," which acts as an entryway through which the virus enters human cells. When the D-peptide binds to it, it fills the pocket and prevents HIV from getting in.

The pocket was discovered in the late 1990s, and researchers ever since have been looking for ways to inhibit it. This, says Kay, is the first time researchers have succeeded.

Kay started working on the project as a post-doctoral researcher at MIT eight years ago. He continued the work when he came to the U. six years ago. They are not at the "end of the lab stage. We've done everything we can do there." The next step will be preclinical testing using animal models and studies to examine issues such as toxicity. In a couple of years, Kay predicts, human clinical trials can begin.

There are a couple of ways the D-peptides might fight HIV infection. The most exciting, Kay says, is its potential as a microbicide that could be applied as a topical prophylactic, primarily for women.

Because of the peptide's structure, it's also possible it could one day be developed into an ingestible prevention or treatment. Peptides normally degrade rapidly in the body, so if you swallow them, the stomach consumes them pretty quickly. But the D-peptides, which are artificial, not natural, are a mirror image of what the body's used to, and it doesn't know how to break them down, offering the possibility they could be an effective tool in an ingestible form. The expectation, Kay says, is that they would survive the body's normal degradation process for "dramatically longer."

The ultimate, scientists agree, would be an HIV vaccine, but there isn't one yet and "there's no clear path" to creating one, Kay says. "Rather than wait for the ultimate solution, you do what you can to protect people."