Long-term Objectives: In response to RFA-AT-05-004, """"""""The Use of Complementary and Alternative Medicine in the Management of HIV/AIDS"""""""", Baylor College of Medicine proposes to explore the potential use of green tea flavanoids as complementary and alternative medicine (CAM) by first studying their molecular properties in preventing the attachment of the HIV virions to susceptible CD4+ T cells. By virtue of the funding of the Pediatric AIDS Clinical Trials Group (AI27551, WT Shearer, Principal Investigator) and the Center for AIDS Research (AI36211, JS Butel, Principal Investigator), Baylor qualifies as an eligible site. Dr. Nance will serve as principal investigator, Dr. William T. Shearer and Dr. Theron G. McCormick as co-investigators and Dr. Michael P. Williamson, University of Sheffield, UK, as consultant. As a basic science R21 application, the grant proposal will request support ($125,000/year) for two years.
Specific Aim 1 : Demonstrate the binding of the green tea flavanoid, epigallocatechin gallate (EGCG) to the CD4 molecule;
Specific Aim 2 : Obtain structural data on the interaction of EGCG by modelling and crystal structure;
Specific Aim 3 : Evaluate the possibility of using EGCG as a CAM in the inhibition of HIV binding to CD4;
Specific Aim 4 : Determine if EGCG at physiological levels (drinking 2 cups of green tea) exerts harmful effects upon normal immune responses in vitro. Methods: Technologies to examine whether EGCG could be used in HIV infection will be: computational and molecular modelling, nuclear magnetic resonance spectroscopy, X-ray crystallography, flow cytometry, enzyme-linked immuno-absorbance assay, and lymphoproliferation. As recent research has been aimed at using small molecules to inhibit HIV-1 viral entry into cells, it is hoped that the further development of EGCG as a therapeutic agent could effectively participate in this capacity. Furthermore, knowledge of the binding mechanism is expected to provide the construct for future usage of EGCG in the clinical management of HIV-1 infection in concert with conventional antiretroviral therapy.
| Nance, Christina L; Siwak, Edward B; Shearer, William T (2009) Preclinical development of the green tea catechin, epigallocatechin gallate, as an HIV-1 therapy. J Allergy Clin Immunol 123:459-65 |
