Ebola virus envelope glycoprotein (GP) (EBOV GP)

The Ebola virus envelope glycoprotein (GP) is the primary protein on the surface of the Ebola virus virion and is essential for viral pathogenesis [4, 8]. It is synthesized as a precursor and cleaved by host furin into GP1 and GP2 subunits, which form a trimeric spike that mediates attachment, endocytic entry, and membrane fusion [5, 13]. Within the host endosome, the GP1 subunit binds to the host receptor Niemann-Pick C1 (NPC1) after being primed by host cathepsins, while the GP2 subunit contains a critical internal fusion loop (FL) [6, 7]. The fusion loop is a hydrophobic domain that, upon a low-pH trigger, undergoes a major conformational change to insert into the host endosomal membrane, facilitating the release of the viral nucleocapsid into the cytoplasm [1, 12]. Due to its indispensable role in infection, the GP is the primary target for several FDA-approved monoclonal antibody treatments, such as Inmazeb (atoltivimab, maftivimab, and odesivimab) and Ebanga (ansuvimab) [3, 18]. These drugs typically work by binding to the glycoprotein to block receptor interaction or to lock the protein in a prefusion state, thereby preventing the fusion loop from initiating membrane merger [9, 14, 21].

Other names

GPGP1,2Ebola virus surface glycoproteinEbola virus spike proteinGlycoprotein subunit 2 fusion loopInternal fusion loop (IFL)

Inhibition of viral entry and membrane fusion by blocking receptor binding or preventing the conformational changes required for fusion loop insertion.