Entry Inhibitors

Overview

Drugs in this class of antiretroviral (ARV) drugs inhibits viral binding or fusion of HIV to host target cells. Binding of the viral envelope glycoprotein (gp)120 to the CD4 receptor induces conformational changes that enable gp120 to interact with a chemokine receptor such as CCR5 or CXCR4 on the host cell; binding of gp120 to the co-receptor causes subsequent conformational changes in the viral transmembrane gp41, exposing the fusion peptide of gp41, which inserts into the cell membrane. A helical region of gp41, called HR1, then interacts with a similar helical region, HR2, on gp41, resulting in a zipping together of the two helices and mediating the fusion of cellular and viral membranes. Enfuvirtide, which requires subcutaneous (SQ) administration, is a synthetic 36-amino-acid peptide derived from a naturally occurring motif within the HR2 domain of viral gp41, and the drug binds to the HR1 region, preventing the HR1-HR2 interaction and correct folding of gp41 into its secondary structure, thereby inhibiting virus-cell fusion. Enfuvirtide was approved for use in combination with other ARV drugs to treat advanced HIV infection in adults and children aged 6 years or older. Maraviroc interferes with viral entry at the chemokine co-receptor level; it is a CCR5 co-receptor antagonist approved for combination therapy for HIV infection in adults infected with CCR5-tropic virus.

Enfuvirtide (Fuzeon, T-20)
Maraviroc (Selzentry, MVC)