Ebola virus glycoprotein GP1,2 stalk-membrane proximal external region (EBOV GP MPER) (EBOV GP MPER)

The Ebola virus glycoprotein GP1,2 stalk-membrane proximal external region (MPER) is a highly conserved and functionally essential segment of the GP2 subunit of the Ebola virus surface glycoprotein (Nature, 2019). This region serves as a critical hinge between the heptad repeat 2 (HR2) domain and the transmembrane anchor, facilitating the dramatic conformational changes required for viral-host membrane fusion (Cell Host & Microbe, 2017). During the fusion process, the MPER participates in the formation of a six-helix bundle, a structural hallmark of class I fusion proteins that drives the merger of the viral envelope with the host endosomal membrane (PLOS Pathogens, 2021). Because the MPER sequence is highly conserved across different ebolavirus species, it is a primary target for the development of broadly neutralizing antibodies (bNAbs) that can neutralize multiple strains, including Zaire, Sudan, and Bundibugyo viruses (Nature, 2019). While currently approved monoclonal antibody therapies like Inmazeb and Ebanga primarily target the receptor-binding site or the glycan cap, research into MPER-targeted agents like BDBV223 aims to provide a universal therapeutic approach (Nature, 2019). Targeting this region effectively arrests the virus in a pre-fusion or intermediate state, preventing the release of the viral genome into the host cell (Cell Reports, 2016). This makes the MPER a high-priority target for next-generation vaccines and immunotherapeutics designed to combat future outbreaks of diverse filoviruses (NIH, 2023).

Other names

Ebola virus GP2 MPEREbola virus glycoprotein stalk regionEBOV GP HR2-MPER regionMembrane-proximal external region of Ebola virus GP

Inhibition of viral-host membrane fusion by preventing the formation of the post-fusion six-helix bundle and blocking structural transitions in the GP2 subunit.