Zaire ebolavirus glycoprotein 1,2 (GP1,2) ectodomain, beta17-beta18 loop region (EBOV GP1,2 beta17-beta18 loop)

The Zaire ebolavirus GP1,2 ectodomain – beta17–beta18 loop region is a critical structural component of the Ebola virus surface glycoprotein (GP), which is the sole protein responsible for viral attachment, endosomal entry, and membrane fusion [1, 16]. This loop, located within the glycan cap of the GP1 subunit, acts as a gatekeeper by occupying a highly conserved hydrophobic pocket, known as the 3_10 pocket, at the base of the GP1–GP2 interface in the prefusion state [2, 7]. This region is a major site of vulnerability for broadly neutralizing antibodies (bNAbs) because the residues within the pocket and the loop are highly conserved across different ebolavirus species [2, 15]. Drugs targeting this region, such as the experimental monoclonal antibodies ADI-15946, EBOV-520, and EBOV-515, work by displacing or mimicking the beta17–beta18 loop to bind the underlying 3_10 pocket [2, 7, 14]. This binding locks the glycoprotein in its prefusion conformation, effectively preventing the conformational changes required for fusion with the host endosomal membrane [7, 11]. Because this epitope is often shielded by the glycan cap and the loop itself in the native trimer, it represents a cryptic target that becomes more accessible after proteolytic processing by host cathepsins [2, 7]. Targeting this specific loop region is a key strategy for developing pan-ebolavirus therapeutics capable of providing broad protection against multiple strains of the virus [2, 15].

Other names

3_10 pocketGP1-GP2 base epitopebeta17-beta18 loopGlycoprotein base regionGP1-GP2 interface base

Neutralization of viral entry by binding to the conserved 3_10 pocket and displacing the beta17-beta18 loop, thereby preventing the conformational transitions necessary for membrane fusion.