Ebola virus envelope glycoprotein GP1 receptor-binding domain (GP1 RBD)

The Ebola virus envelope glycoprotein (GP) is the sole protein on the viral surface responsible for attachment, receptor binding, and membrane fusion (UniProt P87666). It is synthesized as a precursor that is cleaved into GP1 and GP2 subunits, which remain disulfide-linked. The GP1 subunit contains the receptor-binding domain (RBD), which is critical for the virus's ability to infect host cells (PubMed: 21866103). After the virus is internalized into the endosome, the GP1 subunit is proteolytically processed by host cathepsins to expose the RBD. The exposed RBD then binds to the host endosomal receptor Niemann-Pick C1 (NPC1), a prerequisite for viral membrane fusion (PubMed: 21866102). This binding event triggers conformational changes in the GP2 subunit that allow the viral genome to enter the cytoplasm. Because of its essential role in the viral life cycle, the GP1 RBD is a primary target for neutralizing monoclonal antibodies and vaccine development. Therapeutic drugs like Ansuvimab and the components of the Inmazeb cocktail (Atoltivimab, Maftivimab, and Odesivimab) work by binding to this domain or adjacent regions to block receptor interaction (FDA: Ebanga, Inmazeb). These treatments have been shown to significantly reduce mortality in patients infected with Zaire ebolavirus. Monitoring viral load and GP-specific antibody responses is essential for evaluating the efficacy of these RBD-targeted therapies.

Other names

GP1 subunitEBOV GP1Receptor-binding domain of GP1Ebola virus GP1 RBD

Neutralization of viral particles by blocking the interaction between the GP1 receptor-binding domain and the host cell receptor Niemann-Pick C1 (NPC1), thereby preventing viral entry and infection.