The catechin, epigallocatechin gallate (EGCG), the active component of green tea, has anti-inflammatory, anti-tumorigenic, and anti-oxidative as well as anti-viral properties. In vitro, EGCG inhibits HIV-1 replication by the inhibition of HIV-1 reverse transcriptase with a resultant lowered p24 antigenemia. Recently, EGCG has been linked with interference of gp120 binding to CD4. We propose a model of EGCG binding to the CD4 molecule with competitive inhibition of HIV-1-gp120 binding.

Previously generated NMR spectroscopy and time-averaged nuclear Overhauser effects of EGCG protein chemistry were utilized in the development of multiple EGCG molecular conformations. Using the protein database file 1CDJ, the molecular structure of CD4 was illustrated via electron density mapping at 3A. Modeling of EGCG binding to CD4 was achieved by computer-generated docking programs.

Specific residues of the D1 domain of the CD4 molecule involved in HIV-1-gp120 binding were demonstrated to be potential sites of EGCG binding. Analysis of the residues involved in the binding of HIV-1-gp120 to the CD4 molecule revealed a binding pocket of amino acids, flanked by Phe43 and Arg59. The inherent conformational flexibility of EGCG lends itself to binding with this region of critical residues.

Mechanisms that interfere with the interaction of HIV-1-gp120 and CD4+ T cells have been purported as potential targets in HIV-1 treatment. We present a model of EGCG binding to a pocket of the CD4 molecule that might result in the interference of HIV-1-gp120 binding and subsequent inhibition of HIV-1 infection of CD4+ T cells.