Zaire ebolavirus glycoprotein internal fusion loop (EBOV GP IFL) (EBOV GP IFL)

The Zaire ebolavirus glycoprotein internal fusion loop (IFL) is a highly conserved, hydrophobic region located within the GP2 subunit of the Ebola virus (EBOV) spike protein (UniProt: P87666). It plays a pivotal role in the viral entry process by mediating the fusion between the viral envelope and the host cell endosomal membrane (PubMed: 27184314). Following macropinocytosis and proteolytic priming of the GP1 subunit by host cathepsins to expose the receptor-binding domain for Niemann-Pick C1 (NPC1), the IFL is projected toward and inserts into the host membrane. Because of its essential role in membrane fusion and its high degree of sequence conservation among filoviruses, the IFL is a primary target for the development of neutralizing monoclonal antibodies and fusion-inhibiting small molecules (PubMed: 29109255). Therapeutic agents targeting this site, such as the antibodies ADI-15878 and CA45, typically function by preventing the structural rearrangement of GP2 into its post-fusion six-helix bundle state. This action effectively traps the virus within the endosome and prevents the infection of the host cell (PubMed: 28100724). The high conservation of this loop suggests that therapies targeting it may provide broad protection against multiple ebolavirus species.

Other names

Ebola virus GP2 fusion loopGP2 internal fusion loopEBOV GP-IFLEbolavirus fusion peptideGP2-IFL

Neutralization of viral infectivity by binding to the GP2 internal fusion loop, thereby preventing its insertion into the host endosomal membrane and inhibiting the conformational change required for membrane fusion (PubMed: 28100724).