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

The Respiratory Syncytial Virus (RSV) fusion (F) protein is a critical class I viral fusion glycoprotein that mediates the fusion of the viral envelope with the host cell membrane (UniProt P03420). It exists in a metastable prefusion (pre-F) conformation and a stable postfusion (post-F) conformation. The prefusion-stabilized form is the most effective target for vaccines and monoclonal antibodies because it displays highly potent neutralizing epitopes, such as Site Ø and Site V, which are absent in the postfusion form (McLellan et al., 2013). Stabilization of this protein, often achieved through structure-based design like the DS-Cav1 mutations, allows for the induction of high-titer neutralizing antibodies (Graham, 2017). This target is the basis for recently approved vaccines like Arexvy and Abrysvo, and long-acting monoclonal antibodies like Nirsevimab, designed to prevent severe lower respiratory tract disease in infants and older adults (FDA, 2023). By maintaining the protein in its prefusion state, these therapeutics effectively block the virus from entering host cells and initiating infection.

Other names

RSV F proteinFusion glycoproteinPre-FDS-Cav1RSV-F

Neutralization of viral entry by binding to the prefusion conformation of the F protein, thereby preventing the structural transition to the postfusion state required for membrane fusion (McLellan et al., 2013; Graham, 2017).