Envelope glycoprotein (GP) (EBOV GP)

The Ebola Zaire virus glycoprotein (EBOV GP) is the primary surface protein of the Ebola virus and the critical mediator of viral entry into host cells [4, 8]. It is expressed as a trimeric spike composed of two subunits, GP1 and GP2, which are generated by furin cleavage of a precursor polyprotein [9, 13]. GP1 facilitates initial attachment to host cell surface factors and subsequent binding to the endosomal receptor Niemann-Pick C1 (NPC1) after proteolytic priming by host cathepsins [4, 13]. GP2 acts as a class I viral fusion protein, driving the fusion of the viral envelope with the host endosomal membrane to release the viral genome into the cytoplasm [8, 10]. Beyond its role in entry, EBOV GP contributes to pathogenesis by down-regulating host cell surface molecules like integrins and MHC class I, leading to vascular leakage and immune evasion [14, 16]. It also produces a secreted isoform (sGP) that serves as an antigenic decoy to subvert the host immune response [12, 15]. Due to its essential functions, EBOV GP is the main target for FDA-approved monoclonal antibodies such as those in Inmazeb and Ebanga, as well as the primary component of the Ervebo vaccine [3, 5, 23].

Other names

GP1,2GP1GP2sGPssGPshed GPZaire ebolavirus glycoproteinEbola Zaire virus glycoprotein

Monoclonal antibodies bind to specific epitopes on the GP1 or GP2 subunits, neutralizing the virus by blocking attachment to host receptors like NPC1 or inhibiting the membrane fusion process [3, 5]. Some experimental small molecules bind to a cavity in the GP trimer to destabilize the prefusion conformation and prevent viral entry [2, 6].