Question

What are the three drug inhibitors that interfere with the key steps of HIV replication?

Answer 1

Fusion Inhibitors, CCR5 Blockers, and Low-Molecular-Weight Inhibitors. Fusion inhibitors and CCR5 antagonists inhibit HIV entry into host cells.

Fusion inhibitors bind to viral gp41 and block the conformational changes necessary to induce fusion of the viral particle with the host cell. CCR5 antagonists bind to the CCR5 chemokine coreceptor on host cells, induce a conformationalchange that impedes CCR5 interaction with HIV gp120, thereby preventing HIV entry into host cells.

Small molecular weight inhibitors of HIV binding to the CD4 molecule are a new approach. Epigallocatechin gallate (EGCG), by blocking gp120 binding to the CD4 molecule, has been shown to inhibit the infections of CD4 T cells in culture by wild type viruses, setting the stage for a Phase I/II study in humans .Recent studies indicate that polyphenolic EGCG, a component of green tea, can bind to the HIV binding site of CD4 (KD = 10nM as measured by nuclear magnetic spectroscopy) and potentially interfere in viral infection by interaction with 3 key amino acids in the D1 domain of the CD4 molecule (tryptophane 62, phenylalanine 43 , and arginine 59).