Ebola virus glycoprotein glycan cap (EBOV GP glycan cap)

The Ebola virus glycoprotein (GP) is the primary surface protein of the Ebola virus, essential for host cell attachment and membrane fusion (Murin et al., 2014, PNAS). The glycan cap is a specific domain within the GP1 subunit that covers the receptor-binding site (RBS), acting as a shield against the host immune system (Davidson et al., 2015, J. Virol.). The 1H3 epitope refers to the specific binding site on the glycan cap recognized by the monoclonal antibody 1H3, which is a component of the ZMapp treatment (Qiu et al., 2014, Nature). Binding to this epitope can interfere with the proteolytic processing of the glycoprotein by host cathepsins in the endosome, a step required to expose the RBS for binding to the NPC1 receptor (Bornholdt et al., 2016, Science). Furthermore, antibodies targeting this region often utilize Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), to clear the infection (Gunn et al., 2018, Cell Host & Microbe). Targeting the glycan cap is a proven strategy for neutralizing the virus, though the high rate of mutation in viral glycoproteins requires constant monitoring for escape variants.

Other names

Ebola virus GP1 glycan cap1H3 epitopeEBOV GP glycan capEbola virus glycoprotein subunit 1 glycan cap

The 1H3 antibody binds to the glycan cap of the Ebola virus glycoprotein (GP1), which normally shields the receptor-binding site. Binding can inhibit the proteolytic cleavage of the glycan cap by host cathepsins, a necessary step for viral entry, and facilitates immune-mediated clearance of the virus through Fc-effector functions (Murin et al., 2014, PNAS; Qiu et al., 2014, Nature).