Ebolavirus glycoprotein base region, quaternary GP1–GP2 epitope (EBOV GP base region)

The Ebolavirus glycoprotein (GP) is the sole protein expressed on the surface of the Ebola virus and is critical for mediating host cell attachment, endosomal entry, and membrane fusion (Lee and Saphire, 2009). The base region of the GP is a highly conserved quaternary epitope situated at the interface of the GP1 and GP2 subunits, near the viral membrane (Lee et al., 2008). This region functions as a structural clamp that maintains the GP trimer in its metastable prefusion conformation (Stanford.edu). Therapeutic monoclonal antibodies targeting this epitope, such as maftivimab (a component of the FDA-approved Inmazeb cocktail) and the antibodies 2G4 and 4G7 (components of ZMapp), bind across the GP1–GP2 interface (NIH.gov; FDA.gov). This binding prevents the necessary structural rearrangements and proteolytic priming by host cathepsins required for the virus to fuse with the endosomal membrane (MDPI.com). Due to its essential role in the viral life cycle and high degree of conservation, the GP base region is a primary focus for the development of neutralizing antibody therapies and vaccines against multiple ebolavirus species (Frontiersin.org).

Other names

GP base regionGP1–GP2 interfaceGP base subdomainquaternary GP1–GP2 epitopeGP base epitopeGP waist

Inhibition of viral entry and membrane fusion by stabilizing the prefusion glycoprotein conformation and blocking proteolytic cleavage.