Zaire ebolavirus glycoprotein (GP) (EBOV GP)

The Zaire ebolavirus glycoprotein (GP) is the primary antigen and the only virally encoded protein expressed on the surface of the Ebola virus virion [9, 18]. It exists as a trimer of heterodimers, each composed of a GP1 subunit responsible for host cell attachment and a GP2 subunit that mediates membrane fusion [19]. The glycoprotein is essential for the viral lifecycle, facilitating entry into host cells by binding to the endosomal receptor Niemann-Pick C1 (NPC1) after being cleaved by host proteases such as cathepsins B and L [4, 19]. \n\nBeyond its role in entry, the GP gene also produces soluble forms, such as sGP, which act as immunological decoys to divert the host\'s neutralizing antibody response, a key mechanism of immune evasion [19, 20]. In therapeutic development, the GP is the central target for both vaccines and monoclonal antibody treatments, such as Inmazeb (atoltivimab, maftivimab, and odesivimab) and Ebanga (ansuvimab). These drugs work by binding to conserved epitopes on the GP to block viral entry or flag infected cells for destruction by the host\'s immune system, significantly improving survival outcomes in infected patients [1, 3].

Other names

Ebola virus surface glycoproteinZEBOV GPGP1/GP2Orthoebolavirus zairense glycoproteinGP1,2Soluble glycoprotein (sGP)Small soluble glycoprotein (ssGP)

Monoclonal antibodies target the glycoprotein to neutralize the virus by blocking the receptor-binding domain (RBD) on the GP1 subunit, thereby preventing interaction with the host Niemann-Pick C1 (NPC1) receptor and subsequent viral entry [4, 8]. Additionally, these antibodies can inhibit the GP2-mediated fusion of viral and endosomal membranes or engage host immune effector functions, such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), to eliminate infected cells [1, 10]. Vaccines utilize the glycoprotein as the primary antigen to induce host production of neutralizing antibodies and T-cell mediated immunity to prevent future infections [9, 22].