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

The Respiratory syncytial virus (RSV) prefusion fusion (F) glycoprotein, specifically antigenic site Ø, is a critical target for monoclonal antibodies and vaccine development (McLellan et al., 2013, Science). The F protein is a Class I viral fusion protein that mediates the merger of the viral envelope with the host cell membrane, a process essential for viral entry (Graham, 2017, Immunol Rev). Antigenic site Ø is a highly metastable, neutralization-sensitive epitope located at the apex of the prefusion trimer, which is lost when the protein triggers and rearranges into its postfusion conformation (McLellan et al., 2013, Science). Because antibodies targeting site Ø are significantly more potent than those targeting epitopes shared with the postfusion form, stabilizing the F protein in its prefusion state has been a breakthrough in RSV prevention (Zhu et al., 2017, Sci Transl Med). Therapeutic agents like nirsevimab bind specifically to this site to block the conformational change necessary for infection (Hammitt et al., 2022, N Engl J Med). This target is essential for preventing severe lower respiratory tract disease, such as bronchiolitis and pneumonia, in infants and older adults (FDA, 2023, Beyfortus Approval).

Other names

Site 0Site ZeroRSV pre-F epitope ØRSV F protein prefusion-specific epitopeAntigenic site 0

Neutralization of viral entry by binding to the prefusion conformation of the F protein, preventing the structural transition to the postfusion state required for membrane fusion.