Potential HIV Drug Keeps Virus
Out of Cells
Following up a pioneering 2007 proof-of-concept study, a University of Utah biochemist and colleagues have developed a promising new anti-HIV
drug candidate, PIE12-trimer, that prevents HIV from attacking human cells.
Aug 18, 2010 -SALT LAKE CITY - Following up a pioneering 2007 proof-of-concept study, a University of Utah biochemist and
colleagues have developed a promising new anti-HIV drug candidate, PIE12-trimer, that prevents HIV from attacking human cells.
Michael S. Kay, M.D., Ph.D., associate professor of biochemistry in
the U School of Medicine and senior author of the study published Wednesday, Aug. 18, 2010,
online by the Journal of Virology, is raising funds to begin animal safety studies, followed by human clinical trials in two to three years. Kay
believes PIE12-trimer is ideally suited for use as a vaginal microbicide (topically applied drug) to prevent HIV infection. His research group
is particularly focused on preventing the spread of HIV in Africa, which has an estimated two-thirds of the world's 33 million HIV patients
according to the World Health Organization.
"We believe that PIE12-trimer could provide a major new weapon in the arsenal against HIV/AIDS. Because of its ability to block the virus
from infecting new cells, PIE12-trimer has the potential to work as a microbicide to prevent people from contracting HIV and as a treatment for HIV infected
people. HIV can develop resistance rapidly to existing drugs, so there is a constant need to develop new drugs in hopes of staying ahead of the
virus." Kay said. PIE12-trimer was designed with a unique "resistance capacitor" that provides it with a strong defense against the emergence
of drug-resistant viruses.
Peptide drugs have great therapeutic potential, but are often hampered by their rapid degradation in the body. D-peptides are mirror-image
versions of natural peptides that cannot be broken down, potentially leading to higher potency and longevity in the body. Despite these potential
advantages, no D-peptides have yet been developed.
PIE12-trimer consists of three D-peptides (PIE12) linked together that block a "pocket" on the surface of HIV critical for HIV's gaining entry into the cell.
"Clinical trials will determine if PIE12-trimer is as effective in humans as it is in the lab," Kay said. Across the world, HIV occurs in many different strains and has
the ability to mutate to resist drugs aimed at stopping it. Due to the high conservation of the pocket region across strains, PIE12-trimer worked against all major HIV
strains worldwide, from Southeast Asia and South America to the United States and Africa.
To help advance toward human clinical trials, Kay and co-authors Brett D. Welch, Ph.D., and Debra M. Eckert, Ph.D., research assistant professor
of biochemistry, formed a company, Kayak Biosciences, which is owned by the University of Utah Research Foundation. If PIE12-trimer proves to be an effective
and safe drug against HIV, the same D-Peptide drug design principles can be applied against other viruses, according to Kay. Approval of the first D-peptide
drug would also greatly stimulate development of other D-peptide drugs.
The study's first authors are Welch, and U of U graduate student J. Nicholas Francis. Also contributing were U graduate students Joseph Redman and
Matthew Weinstock, as well as Eckert. Images of how PIE12 binds to the HIV pocket were obtained using X-ray crystallography, a technology that provides
high-resolution analysis of atomic structures, and were provided by Frank Whitby, Ph.D., research assistant professor of biochemistry, and
Christopher P. Hill, Ph.D., professor and co-chair of the Department of Biochemistry. The study includes colleagues from
Thomas Jefferson University in Philadelphia and Monogram Biosciences, South San Francisco, Calif.
This research was funded by the National Institutes of Health and the University of Utah Research Foundation.
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Source: University of Utah Health Care
Reproduced with permission - "University of Utah Health Care "
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