Respiratory syncytial virus fusion glycoprotein (prefusion conformation, antigenic site Ø) (RSV Pre-F Site Ø)

The Respiratory syncytial virus (RSV) fusion (F) glycoprotein is a class I viral fusion protein that mediates viral entry by fusing the viral envelope with the host cell membrane (McLellan et al., 2013, Science). It is synthesized as a metastable prefusion (Pre-F) trimer that undergoes a massive conformational change to a stable postfusion (Post-F) state during the fusion process. Antigenic site Ø is a highly potent neutralizing epitope located at the apex of the Pre-F trimer and is unique to this conformation, as it is lost during the transition to the Post-F state (Graham, 2016, Vaccine). Because site Ø is the target of the most potent naturally occurring neutralizing antibodies, it has become the primary focus for the development of next-generation RSV preventatives. Monoclonal antibodies like nirsevimab and stabilized Pre-F vaccines like Abrysvo and Arexvy specifically target or present this site to provide robust protection against RSV-related bronchiolitis and pneumonia (Zhu et al., 2017, Sci Transl Med). Targeting site Ø is particularly effective because it neutralizes the virus before it can initiate the fusion process, making it a cornerstone of modern RSV immunotherapy and prophylaxis.

Other names

RSV F protein site 0RSV Pre-F site zeroRSV fusion protein antigenic site ØPrefusion-specific epitope Ø

Neutralization of viral infectivity by binding to the prefusion F protein and preventing the conformational change required for membrane fusion (McLellan et al., 2013, Science).