Ebola virus glycoprotein 2 fusion loop (EBOV GP2 FL)

The Ebola virus glycoprotein fusion loop is not a therapeutic drug target in the conventional sense. It is a structural domain of a viral protein, not a human host cell protein or receptor. Drug development focuses on targeting host cell receptors (such as NPC1) or viral entry mechanisms, rather than directly targeting viral protein domains.[1][3] The fusion loop itself is a component of the viral glycoprotein that mediates membrane fusion, but it is not a "target" that drugs interact with—rather, it is a viral component that researchers study to understand viral entry mechanisms for potential therapeutic intervention. The Ebola virus glycoprotein 2 (GP2) fusion loop is a hydrophobic structural domain located within the GP2 subunit of the Ebola virus envelope glycoprotein.[3] Consisting of residues 511–556, the fusion loop contains a series of hydrophobic residues (including leucine, tryptophan, isoleucine, proline, tyrosine, and phenylalanine) bounded by an antiparallel, disulfide-linked β-scaffold structure.[3] In the prefusion state, the fusion loop wraps around the outside of the trimeric GP complex. During viral entry, the fusion loop undergoes conformational changes triggered by low pH in the endosome and receptor binding to Niemann-Pick C1 (NPC1), exposing its hydrophobic residues to penetrate the host cell membrane and initiate membrane fusion.[1][3] The fusion loop directly interacts with the membrane-proximal external region (MPER) of GP2 through critical tryptophan residues (WTGW motif), and this interaction is functionally essential for efficient viral entry and membrane fusion.[1] Mutations disrupting the fusion loop's hydrophobic residues or its interaction with MPER significantly impair viral fusion and cell entry. Research on the fusion loop has been conducted to understand viral entry mechanisms and inform vaccine and therapeutic development strategies, but the fusion loop itself is not directly targeted by therapeutic drugs. Instead, therapeutic approaches may target host cell receptors involved in viral entry or attempt to block viral fusion through other mechanisms.

Other names

Internal fusion loop (FL)Fusion peptideHydrophobic fusion loopEBOV GP2 internal fusion loop

Not applicable (viral structural domain)