Respiratory syncytial virus fusion protein (prefusion state) (RSV pre-F)

The Respiratory syncytial virus (RSV) fusion (F) protein in its prefusion state is the primary target for modern RSV vaccines and monoclonal antibodies. As a class I viral fusion glycoprotein, it mediates viral entry by fusing the viral envelope with the host cell membrane through a massive conformational shift from a metastable prefusion state to a stable postfusion state (McLellan et al., 2013). Antigenic site Ø and site V are highly conserved, potent neutralizing epitopes located at the apex of the prefusion trimer that are absent in the postfusion form (Tian et al., 2017). Drugs like nirsevimab bind to site Ø to lock the protein in its prefusion state, effectively neutralizing the virus before it can infect host cells (Zhu et al., 2017). This target is essential for preventing severe lower respiratory tract disease, such as bronchiolitis and pneumonia, particularly in infants and older adults. Recent clinical successes with prefusion-stabilized vaccines have validated these specific antigenic sites as the most effective targets for eliciting protective immunity.

Other names

RSV F proteinPrefusion F glycoproteinRSV-FAntigenic site ØAntigenic site V

Neutralization of viral infectivity by binding to the prefusion conformation of the F protein, specifically at site Ø or site V, which prevents the structural transition to the postfusion state required for membrane fusion and viral entry (McLellan et al., 2013).