Hendra virus fusion protein (HeV-F)

The Hendra virus fusion protein (HeV-F) is a critical class I viral fusion glycoprotein responsible for mediating the merger of the viral envelope with the host cell plasma membrane. It is synthesized as an inactive precursor, F0, which must undergo proteolytic cleavage by host cell cathepsins into disulfide-linked F1 and F2 subunits to become fusion-competent (UniProt P0C1C6). The protein exists in a metastable prefusion conformation on the virion surface and undergoes a dramatic, irreversible structural rearrangement to a highly stable postfusion state upon triggering by the viral attachment (G) protein (PubMed: 26855425). This conformational change is essential for delivering the viral genome into the host cytoplasm, making HeV-F a primary target for neutralizing antibodies and the development of fusion-inhibitory therapeutics. Hendra virus causes severe, often fatal, respiratory and neurological disease in humans, with case fatality rates exceeding 50% (WHO). Current therapeutic strategies targeting HeV-F focus on monoclonal antibodies that stabilize the prefusion state and synthetic peptides that mimic the heptad repeat regions to block the transition to the postfusion six-helix bundle (PubMed: 31167913).

Other names

Hendra virus prefusion fusion glycoproteinHendra virus F proteinHeV fusion glycoproteinFusion glycoprotein F0Hendra virus F1/F2 subunits

Inhibition of viral-host membrane fusion by stabilizing the metastable prefusion conformation or by binding to the heptad repeat regions to prevent the formation of the postfusion six-helix bundle.