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Peptides discovered by researchers at the University of Utah may lead to the development of new drugs that prevent HIV - the virus that causes AIDS - from entering human cells.
Michael Kay, an assistant professor of biochemistry, and his research team found that the peptides - called "D-peptides" - tightly bind to a structure in HIV called a "pocket," a key component of the virus' machinery that helps it enter cells.
"We're basically making a knob that will fit into that pocket and block binding particles," said Kay, the senior author of a study published this week in Proceedings of the National Academy of Sciences.
Peptides - very short proteins - are natural and artificial compounds, such as hormones and antibiotics. Unlike natural peptides, which the body easily absorbs, manufactured D-peptides may be able to stay in the body longer.
"They are much more durable than natural peptides and have the potential to be taken by mouth," Kay said. "Natural peptides generally make poor drugs because they must be injected and are readily degraded by the body."
While HIV rapidly mutates and can adapt to resist previously effective drugs, Kay said, "a key feature of the current work is our attempt to anticipate and avoid drug resistance. The HIV pocket is similar in all HIV strains and cannot mutate without disrupting HIV's ability to enter cells."
The D-peptides are now being studied in pre-clinical trials, as well as in advanced lab studies, to determine how well the peptides work and whether there is any likelihood of toxicity, Kay said.
The inhibitor drug could be tested in people within two years.
"The remaining question is, is it safe?" Kay said. "Is it toxic? Is there anything else in the body that might go on that would interfere with its activity?"
If proven safe and effective, D-peptides could suppress HIV in those who have it, by preserving their immune cells, and prevent its transmission to those who are not infected, he said.
These inhibitors could be used as microbicides - topically applied drugs used during sexual intercourse that prevent the spread of HIV infection. Such a drug could be cost effective and help save lives in the developing world, he said.
Kay said while D-peptide design is in its infancy, he's hopeful it will stimulate development of D-peptide therapeutics for other viruses that enter cells in the same way as HIV, including Ebola and influenza.
The research was funded by the National Institutes of Health, the University of Utah Research Foundation and the American Cancer Society.