Zaire ebolavirus glycoprotein internal fusion loop (EBOV GP IFL)

The Zaire ebolavirus glycoprotein internal fusion loop (IFL) is a critical functional domain within the GP2 subunit of the viral envelope glycoprotein complex (GP1,2). Unlike many other class I fusion proteins that utilize a terminal fusion peptide, ebolaviruses employ this internal loop (residues 511–556), which features a hydrophobic tip that inserts into the host endosomal membrane to initiate fusion. This process occurs after the virus is internalized via macropinocytosis and the GP1 subunit is proteolytically primed by host cathepsins to expose the fusion machinery. The IFL is a primary target for therapeutic intervention because its conservation across different ebolavirus species makes it a site of vulnerability for broadly neutralizing antibodies like ADI-15878 and CA45. Additionally, small molecules such as toremifene and certain antidepressants have been shown to bind within a pocket associated with the IFL, destabilizing the pre-fusion trimer and preventing the conformational changes necessary for infection.

Other names

Ebola virus GP2 internal fusion loopEBOV GP fusion peptide regionEbolavirus internal fusion loopGP2 IFLZaire ebolavirus GP1,2 ectodomain internal fusion loop

Inhibition of viral-host membrane fusion by stabilizing the pre-fusion conformation of the glycoprotein and preventing the insertion of the hydrophobic fusion loop into the host endosomal membrane.