Respiratory syncytial virus fusion protein (prefusion conformation), antigenic site Ø (RSV PreF site Ø)

The Respiratory syncytial virus (RSV) fusion (F) protein is a class I fusion glycoprotein essential for viral entry, mediating the fusion of viral and host cell membranes. It exists in a metastable prefusion (PreF) conformation on the virion surface before triggering, after which it undergoes a massive structural rearrangement into a stable postfusion (PostF) state. Antigenic site Ø (site zero) is a highly potent neutralizing epitope located at the apex of the PreF trimer, composed of residues from the F1 and F2 subunits (specifically residues 62-69 and 196-209). This site is exclusive to the prefusion conformation and is the primary target for the most potent neutralizing antibodies elicited during natural infection or vaccination. Monoclonal antibodies like nirsevimab bind to site Ø and lock the protein in its prefusion state, preventing the conformational change necessary for membrane fusion. Similarly, next-generation RSV vaccines are engineered to stabilize the PreF conformation to preserve site Ø, ensuring the induction of high-titer neutralizing antibodies. Targeting site Ø has revolutionized RSV prevention, offering significantly higher potency compared to older therapies that targeted epitopes shared with the postfusion form.

Other names

Antigenic site zeroSite ØRSV F protein site ØRSV prefusion F protein site ØRSV PreF site Ø

Fusion inhibition; Neutralization; Passive immunization; Active immunization