Ebolavirus glycoprotein GP1 glycan cap epitope (GP1 glycan cap)

The Ebolavirus glycoprotein GP1 glycan cap epitope is a critical structural domain on the surface of Zaire ebolavirus (EBOV) and Bundibugyo ebolavirus (BDBV) GP trimers. This epitope is heavily glycosylated, forming a "glycan shield" that protects the conserved receptor-binding site (RBS) from host immune detection (Misasi & Sullivan, 2021). For the virus to infect a cell, the glycan cap must be removed by host endosomal proteases, such as cathepsin B and L, to allow the RBS to bind to the Niemann-Pick C1 (NPC1) receptor (Bornholdt et al., 2016). Therapeutic monoclonal antibodies, such as Maivimab (a component of Inmazeb) and 13C6 (a component of ZMapp), specifically bind to this glycan cap epitope (Pascal et al., 2020). These drugs work by sterically hindering the proteolytic cleavage of the GP1 subunit or by facilitating antibody-dependent cellular cytotoxicity (ADCC) through the recruitment of immune cells. Targeting the glycan cap is a primary strategy for therapeutic intervention, although the high mutation rate of ebolaviruses can lead to the emergence of escape mutants that no longer bind these antibodies. Research into cross-reactive antibodies targeting the glycan cap on both EBOV and BDBV is ongoing to provide broader protection against different ebolavirus species (Wec et al., 2017).

Other names

GP1 glycan capEbolavirus GP glycan capGlycan cap of GP1 subunitEbolavirus glycoprotein glycan capGP1 glycan cap epitope

Neutralization of viral entry by inhibiting cathepsin-mediated proteolytic cleavage of the GP1 subunit and mediating Fc-receptor-dependent effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).