HIV gp120

Class

Attachment inhibitor

HIV gp120 is a surface glycoprotein on the outer envelope of the human immunodeficiency virus. Together with its partner protein gp41, it forms the spike structure the virus uses to recognize and enter human immune cells, particularly CD4-positive T lymphocytes. Attachment begins when gp120 binds the CD4 receptor on the host cell surface, triggering a conformational change that exposes a site for a second receptor (a chemokine co-receptor), which then allows the viral and cell membranes to fuse and the viral genome to enter. Because this attachment step is the earliest committed event in infection, blocking it prevents the virus from ever gaining entry, offering a mechanism distinct from drugs that act after the virus is already inside the cell (such as reverse transcriptase or integrase inhibitors). Attachment inhibitors that bind gp120 directly interfere with its ability to engage CD4 or to undergo the shape change needed for entry. This mechanism is relevant mainly in chronic HIV infection, particularly for individuals whose virus has become resistant to multiple other antiretroviral drug classes, since a new binding site on gp120 is generally not affected by resistance mutations selected by other mechanisms.