Green tea component blocks HIV cell entry
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_Green tea component blocks HIV cell entry_
(http://www.bcm. edu/fromthelab/ vol06/is2/ 0307-1.html)

Mike Williamson, Ph.D., professor at the University of Sheffield, used a
special nuclear magnetic resonance imaging device to determine the structure of
EGCG, the critical molecule in the studies of green tea. He is shown with the
Mag4, an 800 MHz spectrometer.

A component of green tea called epigallocatechin gallate, or EGCG, blocks the
ability of the human immunodeficiency virus (HIV) to enter the immune system
cells that it subverts and destroys as part of the AIDS process, said
researchers from Baylor College of Medicine and the University of Sheffield in the
United Kingdom, in a report that appears online in the Journal of Allergy
and Clinical Immunology.
Using the tools of computational and structural biology, Christina L. Nance,
Ph.D., and William T. Shearer, M.D., Ph.D., of BCM and Texas Children's
Hospital, and Mike P. Williamson, Ph.D., of the University of Sheffield,
generated a computer model of the structure of the EGCG molecule. By studying the
conformation of the molecule, they were able to find the mechanism by which it
prevents the HIV envelope protein called gp120 from binding to T-cells that
are susceptible to HIV infection. These are called CD4 cells.
Molecule binding site is key
"We found that the EGCG molecule itself binds to the same exact binding
pocket on the CD4 molecule at the site of the same amino acids to which gp120
binds," said Nance, an instructor in the Department of Pediatrics allergy and
immunology at BCM.
"When it binds there, the gp120 envelope protein and thus HIV can't." She
worked with Shearer, chief of the allergy and immunology service at Texas
Children's Hospital and professor of pediatrics at BCM.
Nance determination lauded

Christina L. Nance, Ph.D.

Shearer said it was Nance's determination to show that physiological levels
of EGCG, an amount achieved by drinking just two cups of green tea, caused
inhibition of gp120 binding to CD4+ T cells. Artificially high concentrations of
EGCG placed in test tubes to inhibit binding have no meaning for patients.
It was Nance's ingenuity that brought clinical relevance to this observation,
Shearer said.
EGCG is a small molecule that fits nicely into that niche, Nance said. Now,
she, Dr. Florante Quiocho, professor of biochemistry and molecular biology,
and their colleagues at BCM are trying to get a three-dimensional replica of
the molecule for a definitive determination of EGCG binding and inhibition of
HIV. From that, researchers may be able to model synthetic molecules that
might be even better at inhibiting HIV binding or additives that could make the
EGCG activity more sustainable.
EGCG has already been studied in cancer, she said. Those studies have shown
it to be safe and nontoxic. However, its effect on immunological cells is not
yet determined. She is currently doing studies of those effects in the
laboratory at Texas Children's Hospital.
Value as treatment unproven as yet
If EGCG proves to have value as an HIV treatment, she said, it probably will
not be used alone at least at first. "It would be part of a cocktail of
drugs," she said. Current cocktails fight HIV at different points in its life
cycle.

William T. Shearer, M.D., Ph.D.

The BCM studies with EGCG began when Nance and Shearer, who are also faculty
members in the BCM Graduate School of Biomedical Sciences, reviewed work by
Japanese researchers showing the potential of the molecule to inhibit the
entry of HIV into immune cells with the CD4 marker. They decided to take the work
further with the structural and computational biology studies, and with the
facilities of the National Center for Macromolecular Imaging at BCM of which
Dr. Wah Chiu, professor of biochemistry and molecular biology at BCM, is the
director.
Nance does not recommend that people drink large quantities of green tea with
the expectation that it will prevent infection with HIV. These studies are
designed to determine whether a drug derived from green tea would have that
effect. A Phase I/II clinical trial is being planned using the auspices of the
Clinical Research Core of the Center for AIDS Research (Dr. Janet S. Butel,
director).
Funding for this research came from the National Institutes of Health, the
Pediatric Research and Education Fund at BCM and the David Fund, Pediatric AIDS
Fund and Immunology Research Fund at Texas Children's Hospital and the
Centers for AIDS Research.
(J Allergy Clin Immunol. 2006 Dec;118(6):1369- 74. Epub 2006 Oct 13.)
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