Respiratory syncytial virus fusion glycoprotein (prefusion conformation, subtype A) (RSV F (pre-F))

The Respiratory syncytial virus (RSV) fusion (F) glycoprotein is a type I integral membrane protein that mediates viral entry by fusing the viral envelope with the host cell membrane (UniProt P03420). It is synthesized as a precursor (F0) that is cleaved into F1 and F2 subunits, which assemble into a metastable prefusion trimer (pre-F). Upon triggering, pre-F undergoes a massive, irreversible conformational rearrangement into a stable postfusion (post-F) state to drive membrane fusion. The pre-F conformation is the primary target for the most potent neutralizing antibodies because it displays unique, highly sensitive epitopes like Site Ø and Site V that are lost in the post-F state (McLellan et al., Science, 2013). Subtype A is one of the two major antigenic groups of RSV, and its pre-F structure serves as the basis for several modern therapeutic interventions. Monoclonal antibodies such as nirsevimab specifically target these prefusion epitopes to provide passive immunity, particularly in infants (FDA, 2023). Additionally, prefusion-stabilized F protein vaccines, such as Arexvy and Abrysvo, are designed to elicit a robust neutralizing antibody response in older adults and pregnant individuals (CDC, 2023). Targeting the prefusion state is significantly more effective than targeting the postfusion state, as pre-F specific antibodies possess much higher neutralizing potency. This target is essential for preventing severe RSV-related diseases like bronchiolitis and pneumonia, which are leading causes of hospitalization in infants and the elderly.

Other names

RSV F proteinRespiratory syncytial virus fusion proteinPre-F proteinRSV-F subtype AFusion glycoprotein F0

Binding to highly conserved epitopes (such as Site Ø or Site V) on the prefusion conformation of the F protein to prevent the structural transition to the postfusion state, thereby inhibiting viral-host cell membrane fusion and viral entry.