Ebola virus surface glycoprotein (GP)

The Ebola virus surface glycoprotein (GP) is the sole virally encoded protein displayed on the surface of the Ebola virion, making it the primary mediator of viral entry and a critical target for the host immune response. It is synthesized as a precursor (GP0) that is proteolytically cleaved by host furin into two subunits, GP1 and GP2, which remain linked by a disulfide bond to form a trimeric spike complex. GP1 is responsible for attachment to host cell surface factors and binding to the endosomal receptor Niemann-Pick C1 (NPC1) after being primed by host cathepsins, while GP2 facilitates the fusion of the viral envelope with the host endosomal membrane. Beyond entry, GP plays a significant role in pathogenesis by producing a secreted form (sGP) that acts as an immunological decoy and by utilizing a dense glycan shield to mask neutralizing epitopes. Due to its essential role in infection, GP is the primary target for FDA-approved monoclonal antibody therapies, such as Inmazeb and Ebanga, and is the key immunogen in the Ervebo vaccine.

Other names

Envelope glycoproteinGP1,2Spike glycoproteinGP1/GP2 heterodimersGPssGPShed GP

Neutralization of viral entry by blocking receptor binding, inhibition of cathepsin-mediated GP priming, and prevention of GP2-mediated membrane fusion.