HIV gp41

Class

Fusion inhibitor

HIV gp41 is a viral envelope glycoprotein that mediates fusion of the virus with the membrane of a target cell, the step that allows the viral genetic material to enter and begin infection. Gp41 works together with its partner protein gp120: gp120 first binds a cell-surface receptor and co-receptor, and this triggers gp41 to unfold and refold into a compact six-helix bundle that draws the viral and cell membranes together until they merge. Fusion inhibitors are peptides designed to bind gp41 during this transient unfolded state, before the six-helix bundle forms, and thereby block membrane merger and prevent the virus from ever entering the cell. Because this mechanism acts outside the cell, at the point of viral entry, it is mechanistically distinct from reverse transcriptase, protease, or integrase inhibitors, which act after the virus has already entered. This makes gp41-targeted peptides useful in combination antiretroviral therapy, particularly for individuals whose virus has become resistant to other drug classes, since blocking entry does not rely on the same resistance pathways. The approach broadly matters in HIV treatment strategy wherever an additional, non-overlapping mechanism is needed to suppress viral replication and limit the emergence of resistant viral strains.