Respiratory syncytial virus fusion glycoprotein (RSV F) prefusion conformation Site Ø (RSV PreF Site Ø)

The Respiratory Syncytial Virus (RSV) fusion (F) protein in its prefusion conformation is the primary target for neutralizing antibodies and modern vaccine development (McLellan et al., 2013, Science). Site Ø (Site Zero) is a highly conserved, potent neutralizing epitope located at the apex of the prefusion F trimer (Zhu et al., 2017, Sci Transl Med). This specific site is metastable and is lost when the protein transitions to its postfusion state, a process required for the virus to fuse with the host cell membrane (Tian et al., 2017, Nat Commun). By targeting Site Ø, monoclonal antibodies and vaccine-induced antibodies can effectively lock the F protein in its prefusion state or sterically hinder the fusion process, thereby preventing viral entry. This target is critical for preventing severe lower respiratory tract disease, such as bronchiolitis and pneumonia, particularly in infants and older adults (NIH, 2023). Recent therapeutic breakthroughs, including the monoclonal antibody nirsevimab and several prefusion-stabilized vaccines like Arexvy and Abrysvo, specifically leverage the high vulnerability of Site Ø to provide robust protection against RSV infection (FDA, 2023). Clinical efficacy of drugs targeting this site is often monitored via neutralizing antibody titers, though it can be limited by the emergence of viral variants with mutations in the epitope region.

Other names

Site ZeroSite 0Antigenic site ØRSV F prefusion conformationRSV F Site ØPrefusion-specific epitope Ø

Neutralization of viral infectivity by binding to the prefusion conformation of the F protein, thereby preventing the structural rearrangement into the postfusion state required for membrane fusion and host cell entry.