Ebola virus glycoprotein GP1 head and glycan cap epitope (EBOV GP1 head/GC)

The Ebola virus glycoprotein (GP) is the primary protein on the viral envelope, mediating host cell attachment, fusion, and entry. It exists as a trimer of GP1-GP2 heterodimers, where the GP1 subunit is responsible for receptor binding and the GP2 subunit facilitates membrane fusion. The GP1 subunit is further divided into the base, head, and glycan cap subdomains. The GP1 head contains the receptor-binding site (RBS) for the endosomal receptor Niemann-Pick C1 (NPC1), while the glycan cap and the mucin-like domain (MLD) form a dense glycan shield that protects the RBS from immune recognition. During the viral entry process, host cathepsins in the endosome cleave the glycan cap and MLD to expose the RBS, a step essential for triggering GP2-mediated fusion. Therapeutic monoclonal antibodies, such as ansuvimab and components of the Inmazeb cocktail (atoltivimab and odesivimab), target epitopes within the GP1 head and glycan cap to neutralize the virus by blocking receptor interaction or proteolytic processing, and by enlisting host immune effector functions to clear the infection.

Other names

Ebola virus GP1 head and glycan capEBOV GP1 head/GCEbola virus glycoprotein 1 head and glycan cap domainGP1 head and glycan cap epitope

Neutralization of viral entry by blocking attachment to host cells and binding to the endosomal receptor NPC1; inhibition of host cathepsin-mediated proteolytic cleavage of the glycoprotein; induction of Fc-mediated effector functions, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC).