Ebolavirus glycoprotein fusion loop and adjacent protomer interface (EBOV GP-FL/Interface)

The Ebolavirus glycoprotein (GP) is the primary mediator of viral entry, existing as a trimer of GP1/GP2 heterodimers on the viral envelope (UniProt P87666). The fusion loop, located within the GP2 subunit, is a critical hydrophobic region that must insert into the host's endosomal membrane to facilitate membrane fusion and viral genome release (PubMed: 28818945). The interface between this fusion loop and the adjacent protomer within the GP trimer represents a highly conserved and functionally essential site. Monoclonal antibodies targeting this specific interface, such as ADI-15878 and CA45, act by locking the glycoprotein in its pre-fusion conformation or sterically blocking the fusion loop's movement (Science, 2017, 357(6355); Nature, 2017, 551(7679)). Because the fusion loop sequence is highly conserved across various ebolavirus species (e.g., Zaire, Sudan, Bundibugyo), this site is a premier target for the development of broad-spectrum, pan-ebolavirus therapeutic antibodies. Targeting this interface offers a strategy to overcome the high mutation rates of the virus by focusing on a functionally constrained region (Cell Reports, 2019, 28(13)).

Other names

EBOV GP fusion loopGP1/GP2 interfaceInternal fusion loop (IFL)GP2 subunit fusion peptideEbolavirus GP2 subunit

Inhibition of membrane fusion by stabilizing the pre-fusion conformation and sterically blocking the insertion of the fusion loop into the host endosomal membrane.