Hendra virus fusion glycoprotein F (HeV F)

The Hendra virus fusion glycoprotein F is a critical class I viral fusion protein located on the envelope of the Hendra virus (HeV) [1, 8]. It mediates the fusion of the viral membrane with the host cell plasma membrane, a process essential for viral entry and the subsequent delivery of the viral genome into the host cytoplasm [1, 4]. Synthesized as an inactive precursor (F0), it must undergo proteolytic cleavage by host cell cathepsin L into two disulfide-linked subunits, F1 and F2, to become fusogenic [6, 20]. This activation is triggered by conformational changes in the accompanying attachment glycoprotein (G) upon its binding to host receptors ephrin-B2 or ephrin-B3 [4, 22]. In addition to its role in primary infection, the F protein expressed on the surface of infected cells facilitates cell-to-cell fusion, leading to the formation of multinucleated syncytia, which contributes to tissue necrosis and the severe pathology of HeV infection [1, 15]. Hendra virus is a highly lethal zoonotic pathogen causing severe respiratory disease and fatal encephalitis in humans, with a case fatality rate exceeding 50% [10, 11]. Because of its essential role in the viral life cycle, the F protein is a primary target for the development of vaccines and therapeutic interventions [4, 21]. Experimental treatments include monoclonal antibodies like hu1F5, which cross-reacts with Nipah virus F and neutralizes the virus by stabilizing the prefusion state [11]. Other therapeutic strategies involve fusion-inhibiting peptides that mimic the heptad repeat regions of the protein and small-molecule inhibitors of the activating protease cathepsin L [6, 20].

Other names

Fusion glycoprotein F0Protein FF proteinF0F1/F2 complex

Inhibition of viral-host membrane fusion by stabilizing the prefusion conformation or preventing the formation of the six-helix bundle.