Ebolavirus glycoprotein 2 (GP2) (EBOV GP2)

The Ebolavirus glycoprotein (GP) is the primary surface protein of the Ebola virus, essential for host cell attachment and entry. It exists as a trimer of GP1/GP2 heterodimers, where GP1 mediates attachment to host receptors like NPC1, and GP2 functions as the fusion machinery (UniProt P87666). The fusion process is driven by the GP2 subunit, which contains an internal fusion loop (IFL) and two heptad repeat regions (HR1 and HR2). Upon triggering in the endosome, GP2 undergoes a massive conformational rearrangement where the IFL inserts into the host membrane and the HR regions collapse into a six-helix bundle to facilitate membrane fusion (Lee et al., 2008, Nature). The specific interface between the IFL and HR1 across different protomers has been identified as a critical site of vulnerability for broadly neutralizing antibodies (Wec et al., 2017, Science). Therapeutic agents targeting this site, such as the antibody ADI-15878, work by cross-linking the GP protomers and locking the fusion machinery in a pre-fusion state, thereby preventing viral entry into the cytoplasm (King et al., 2019, Cell Host & Microbe). This target is highly conserved across different Ebolavirus species, making it a prime candidate for pan-ebolavirus countermeasures.

Other names

Ebola virus fusion proteinGP2 subunitInternal fusion loop (IFL) and heptad repeat 1 (HR1) complexEbolavirus fusion machinery

Inhibition of viral-host membrane fusion by blocking the conformational transition of the GP2 subunit and preventing the insertion of the internal fusion loop into the host membrane.