Ebolavirus glycoprotein subunit 2 (GP2) (GP2)

The Ebolavirus glycoprotein subunit 2 (GP2) is the membrane-anchored component of the viral envelope spike, functioning as a class I viral fusion protein [UniProt P87666]. It contains the internal fusion loop (IFL) and the heptad repeat 1 (HR1) region, which are essential for mediating the fusion between the viral envelope and the host cell's endosomal membrane [Lee et al., Nature 2008]. Following the cleavage of the GP1 subunit by host cathepsins and subsequent binding to the Niemann-Pick C1 (NPC1) receptor, GP2 undergoes a dramatic conformational rearrangement. This process drives the IFL into the host membrane and collapses the HR1 and HR2 regions into a six-helix bundle, bringing the membranes together for fusion [Wec et al., Science 2017]. Because these regions are highly conserved across Ebolavirus species, they are primary targets for pan-ebolavirus neutralizing antibodies and experimental fusion inhibitors. Drugs targeting the IFL and HR1 regions, such as odesivimab, work by sterically blocking the fusion machinery or preventing the necessary structural transitions, thereby halting viral entry and infection [FDA Inmazeb Label].

Other names

Ebola virus GP2GP2 subunitEbolavirus fusion proteinInternal fusion loop (IFL)Heptad repeat 1 (HR1)EBOV GP2

Fusion inhibition: Prevents the conformational change of GP2 required for merging the viral envelope with the host endosomal membrane or blocks the insertion of the internal fusion loop into the host membrane [Wec et al., Science 2017].