Ebola virus Zaire glycoprotein GP1,2 (EBOV GP)

The Ebola virus Zaire glycoprotein GP1,2 is the sole viral protein expressed on the surface of the virion, making it the primary mediator of host cell entry and a critical target for the host immune system (UniProt P87666). It is synthesized as a precursor protein that is cleaved by host furin into two subunits, GP1 and GP2, which remain associated as a trimeric spike. GP1 facilitates initial attachment to the host cell surface and subsequently binds to the essential intracellular receptor Niemann-Pick C1 (NPC1) within the endosome (PubMed: 21866102). GP2 then undergoes a dramatic conformational change to catalyze the fusion of the viral envelope with the endosomal membrane, releasing the viral genome into the cytoplasm. Because of its indispensable role in infection, GP1,2 is the target of FDA-approved monoclonal antibodies such as Inmazeb (a cocktail of atoltivimab, maftivimab, and odesivimab) and Ebanga (ansuvimab-zykl) (FDA, 2020). These therapeutics work by binding to specific epitopes on the glycoprotein to neutralize the virus, either by blocking receptor interactions or preventing the fusion process.

Other names

Envelope glycoproteinGP1,2Spike proteinGPZaire ebolavirus GP

Monoclonal antibodies target the GP1,2 protein to neutralize the virus by blocking its attachment to host cell receptors (such as NPC1) or preventing the conformational changes required for membrane fusion. Some antibodies also trigger antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells (PubMed: 30559420).