Ebolavirus glycoprotein (GP) (GP)

The Ebolavirus glycoprotein (GP) is the sole protein expressed on the surface of the ebolavirus virion and is essential for the viral life cycle across species including Zaire (EBOV), Sudan (SUDV), Bundibugyo (BDBV), Taï Forest (TAFV), and Bombali (BOMV). It is synthesized as a precursor that is cleaved into GP1 and GP2 subunits, which form a trimeric spike; GP1 mediates attachment to host cells and binding to the endosomal receptor Niemann-Pick C1 (NPC1), while GP2 facilitates the fusion of the viral and host membranes (UniProt: P87666). As the primary target for neutralizing antibodies, GP is the focus of most therapeutic and vaccine development efforts, including the FDA-approved monoclonal antibody treatments Inmazeb and Ebanga (FDA: 2020). These therapies work by binding to specific epitopes on the GP to block viral entry or trigger immune-mediated clearance of the virus. However, the significant genetic diversity between ebolavirus species and the presence of a secreted decoy form (sGP) present ongoing challenges for the development of universal, pan-ebolavirus medical countermeasures (PubMed: 30541063).

Other names

GP1/GP2 complexEnvelope glycoproteinSpike proteinsGPssGPEbolavirus surface glycoprotein

Monoclonal antibodies target the Ebolavirus glycoprotein to neutralize the virus through several mechanisms: blocking the interaction between the GP1 subunit and the host cell receptor Niemann-Pick C1 (NPC1), inhibiting the conformational changes in the GP2 subunit required for membrane fusion, and promoting the clearance of virions via Fc-mediated effector functions such as antibody-dependent cellular cytotoxicity (ADCC) (PubMed: 30541063, FDA: 2020).