Respiratory syncytial virus prefusion F glycoprotein (subgroup A) (RSV PreF (subgroup A))

The Respiratory syncytial virus prefusion F glycoprotein (subgroup A) is a key surface protein of the RSV-A virus, functioning as a class I viral fusion protein (McLellan et al., 2013). It plays a vital role in the viral life cycle by mediating the fusion of the viral envelope with the host cell membrane, allowing the viral genome to enter the cytoplasm (Pfizer, 2024). The F protein is synthesized as an inactive precursor (F0) that is cleaved into F1 and F2 subunits, which then assemble into a metastable prefusion trimer (NIH, 2024). Upon contact with a host cell, this protein undergoes a dramatic and irreversible conformational change into a stable postfusion state to drive membrane fusion (Creative Diagnostics, 2024). The prefusion conformation is the primary target for therapeutic intervention because it contains highly sensitive neutralizing epitopes, such as Site Ø and Site V, which are absent in the postfusion form (Bioworld, 2023). Modern vaccines and monoclonal antibodies are designed to stabilize or target this specific conformation to prevent infection and reduce the incidence of severe lower respiratory tract diseases, including bronchiolitis and pneumonia, in infants and older adults (MDPI, 2025).

Other names

RSV-A PreFRSV-A fusion proteinRSV-A F proteinRespiratory syncytial virus fusion glycoprotein (prefusion)RSV-A F1/F2 glycoprotein

Vaccines and monoclonal antibodies target the prefusion conformation of the F protein to elicit or provide neutralizing antibodies that block the conformational change required for viral-host membrane fusion, thereby preventing viral entry into respiratory epithelial cells (McLellan et al., 2013; NIH, 2023). Small molecule inhibitors bind to the prefusion trimer to stabilize it and prevent the transition to the postfusion state (Cianci et al., 2004; NIH, 2024).