Hendra virus fusion glycoprotein (HeV F)

The Hendra virus fusion glycoprotein (HeV F) is a critical Class I viral fusion protein located on the envelope of the Hendra virus, a highly lethal zoonotic pathogen. It is synthesized as an inactive precursor (F0) that must be cleaved by host cell proteases, specifically cathepsin L, into its active F1 and F2 subunits to become functional. HeV F exists as a metastable trimer that works in coordination with the attachment (G) glycoprotein; upon the binding of G to host receptors such as Ephrin-B2 or Ephrin-B3, F is triggered to undergo a massive conformational change. This refolding process drives the fusion of the viral and host cell membranes, allowing the viral genome to enter the cytoplasm. Because of its essential role in the viral life cycle, HeV F is a primary target for the development of antiviral therapeutics and vaccines. Modern therapeutic strategies focus on neutralizing monoclonal antibodies, such as hu1F5 and h5B3.1, which recognize conserved epitopes to block membrane fusion, as well as fusion inhibitor peptides derived from the heptad repeat regions of the protein. Successfully targeting HeV F not only prevents initial infection but also inhibits the formation of multinucleated syncytia, a hallmark pathological feature of henipavirus disease in humans and animals.

Other names

Fusion proteinF proteinHendra virus F proteinFusion glycoprotein F0Fusion glycoprotein F1Fusion glycoprotein F2

Inhibition of the conformational transition from a metastable pre-fusion state to a stable post-fusion state by blocking the formation of the six-helix bundle (6HB) or interfering with heptad repeat (HR1/HR2) interactions, thereby preventing viral-host membrane merger.