 Entry inhibitors, also known as fusion inhibitors, are a class of antiretroviral drugs, used in combination therapy for the treatment of HIV infection. This class of drugs interferes with the binding, fusion and entry of an HIV virion to a human cell. By blocking this step in HIV's replication cycle, such agents slow the progression from HIV infection to AIDS
HIV entry
Proteins
There are several key proteins involved in the HIV entry process.
- CD4, a protein receptor found on the surface of helper T cells in the human immune system, also called CD4+ T cells
- gp120, a protein on HIV surface that binds to the CD4 receptor
- CCR5, a second receptor found on the surface of CD4+ cells, called a chemokine co-receptor
- CXCR4, another chemokine co-receptor found on CD4+ cells
- gp41, a HIV protein, closely associated with gp120, that penetrates the cell membrane
Binding, fusion, entry sequence
HIV entry into a human cells requires the following steps in sequence:
1. The binding of HIV surface protein gp120 to the CD4 receptor
2. A conformational change in gp120, which both increases its affinity for a coreceptor and exposes gp41
3. The binding of gp120 to a coreceptor either CCR5 or CXCR4
4. The penetration of the cell membrane by gp41, which approximates the membrane of HIV and the T cell and promotes their fusion
5. The entry of the viral core into the cell
Entry inhibitors work by interfering with one aspect of this process. |
