Ebola virus envelope glycoprotein GP1 subunit (GP1)

The Ebola virus envelope glycoprotein GP1 subunit is the surface-exposed component of the trimeric GP complex responsible for viral attachment and entry into host cells. It is generated through the proteolytic cleavage of the GP0 precursor by furin into GP1 and GP2 subunits, which remain linked by a disulfide bond. GP1 contains the receptor-binding domain (RBD) that interacts with the intracellular host receptor Niemann-Pick C1 (NPC1) after the virus is internalized into endosomes and the glycan cap is removed by host cathepsins. Beyond its role in entry, GP1 is heavily glycosylated, forming a glycan shield that helps the virus evade the host immune system by masking conserved epitopes from neutralizing antibodies. As the primary target for the host humoral immune response, GP1 is the focal point for therapeutic intervention and vaccine development. Modern monoclonal antibody treatments, such as Ansuvimab (Ebanga) and the components of Inmazeb (Atoltivimab, Maftivimab, and Odesivimab), specifically target epitopes on GP1 to neutralize the virus and prevent infection of new cells. These therapies have significantly improved survival rates in patients with Ebola virus disease. However, the high mutation rate of RNA viruses like Ebolavirus poses a continuous challenge, as changes in the GP1 sequence can lead to the emergence of escape mutants that bypass existing treatments. (Sources: UniProt P87666; PubMed: 33091367, 30540912; NIH/NIAID).

Other names

GP1 subunitEBOV GP1Surface glycoprotein GP1Attachment protein GP1

Monoclonal antibodies bind to specific epitopes on the GP1 subunit to neutralize the virus by blocking its attachment to host cell receptors (such as NPC1) or preventing the conformational changes required for membrane fusion, thereby inhibiting viral entry into the host cell.