Zaire ebolavirus envelope glycoprotein and soluble glycoprotein (EBOV GP/sGP)

The Zaire ebolavirus envelope glycoprotein (GP) is the primary protein expressed on the virion surface and is essential for the viral life cycle, mediating attachment, endocytosis, and membrane fusion with host cells (UniProt P87666). It is synthesized as a precursor (GP0) that is cleaved by host furin into GP1, responsible for receptor binding, and GP2, which facilitates fusion with the endosomal membrane via interaction with the Niemann-Pick C1 (NPC1) receptor (PubMed: 21866103). A unique feature of the ebolavirus genome is the production of a secreted, non-structural soluble glycoprotein (sGP) through transcriptional editing; sGP shares the N-terminal sequence with GP and acts as an immune decoy to subvert the host's humoral response by absorbing neutralizing antibodies (PubMed: 16227264). Because of its critical role in infection, GP is the primary target for therapeutic interventions, including the recombinant viral vaccine Ervebo and monoclonal antibody treatments like Inmazeb (atoltivimab, maftivimab, and odesivimab) and Ebanga (ansuvimab) (FDA, 2020). These therapies work by binding to conserved epitopes on GP to neutralize the virus and prevent its spread within the host. Monitoring for antigenic drift is crucial, as mutations in the GP gene can lead to reduced efficacy of these targeted biologics (PubMed: 30531979).

Other names

GPsGPGP1/GP2 complexSpike proteinEbolavirus glycoproteinPre-fusion GP trimer

Monoclonal antibodies target specific epitopes on the GP1 or GP2 subunits of the glycoprotein complex. For example, ansuvimab binds to the receptor-binding domain of GP1, directly blocking the interaction with the host endosomal receptor Niemann-Pick C1 (NPC1) (FDA Ebanga Label; PubMed: 21866103). Other antibodies, such as those in the Inmazeb cocktail, bind to distinct, non-overlapping epitopes to neutralize the virus by preventing the conformational changes required for membrane fusion or by triggering effector functions like antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells (FDA Inmazeb Label; PubMed: 30531979).