Zaire ebolavirus glycoprotein (EBOV GP) (EBOV GP)

The Zaire ebolavirus glycoprotein (EBOV GP) is the sole protein expressed on the surface of the Ebola virus virion and is essential for viral attachment, fusion, and entry into host cells (UniProt P87666). It is synthesized as a precursor that is cleaved into GP1 and GP2 subunits, which form a trimeric spike on the viral envelope. The receptor-binding site (RBS) is located within the GP1 subunit and is initially sequestered by a glycan cap and mucin-like domain to evade immune detection. Upon viral internalization into host endosomes, proteolytic processing by cathepsins B and L removes these protective layers, exposing the RBS for binding to the host intracellular receptor Niemann-Pick C1 (NPC1) (PubMed: 21866103, 21866102). This binding event triggers GP2-mediated fusion of the viral and endosomal membranes, releasing the viral genome into the cytoplasm. Therapeutic monoclonal antibodies, such as Ansuvimab (Ebanga) and the components of the REGN-EB3 cocktail (Inmazeb), specifically target the GP to neutralize the virus by blocking the RBS-NPC1 interaction or stabilizing the prefusion state (PubMed: 31774950, FDA 2020). These interventions have become the standard of care for reducing mortality in patients infected with Zaire ebolavirus.

Other names

Ebola virus glycoproteinGP1/GP2 complexEBOV GP receptor-binding siteEBOV GP RBSZaire ebolavirus GP

Neutralization of viral entry by sterically blocking the interaction between the glycoprotein receptor-binding site and the host cell receptor Niemann-Pick C1 (NPC1) or by preventing the conformational changes required for membrane fusion.