Ebola virus glycoprotein, cleaved form (GPcl) (GPcl)

The Ebola virus glycoprotein, cleaved form (GPcl), is a proteolytically processed version of the viral surface glycoprotein (GP) that is essential for the infection of host cells [UniProt P87666]. During the viral entry process, the Ebola virion is internalized into host endosomes where the full-length GP is cleaved by host proteases, such as cathepsins B and L, to remove the glycan cap and the mucin-like domain [PMID: 16121184]. This cleavage event generates the GPcl form, which consists of a 19 kDa GP1 subunit and a 25 kDa GP2 subunit, effectively exposing the receptor-binding domain (RBD) that was previously shielded [PMID: 21866103]. The primary biological role of GPcl is to bind to the intracellular host receptor Niemann-Pick C1 (NPC1) within the endolysosomal compartment, a critical step that triggers the fusion of the viral envelope with the host cell membrane [PMID: 21866103]. Because this interaction is mandatory for viral escape into the cytoplasm, GPcl is a major target for therapeutic intervention. Monoclonal antibodies like Ansuvimab (mAb114) and Maftivimab (a component of Inmazeb) specifically target the exposed RBD of GPcl to neutralize the virus [PMID: 30643263]. Challenges in targeting GPcl include the necessity for therapeutic agents to reach the acidic endosomal environment and the potential for the virus to develop escape mutations within the highly conserved RBD [PMID: 31434733].

Other names

Primed Ebola virus glycoproteinGP19/GP17 complexEndosomally processed Ebola glycoproteinGP1/GP2 cleaved formCathepsin-cleaved Ebola glycoprotein

Blocking the interaction between the exposed receptor-binding domain (RBD) of the cleaved glycoprotein and the host endosomal receptor Niemann-Pick C1 (NPC1), thereby preventing viral-host membrane fusion and subsequent viral entry into the cytoplasm [PMID: 30643263, PMID: 21866103].