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

The Respiratory syncytial virus (RSV) fusion (F) protein is a type I membrane glycoprotein that is essential for viral entry and syncytia formation [PubMed: 23558174]. It exists in two distinct structural states: a metastable prefusion conformation (pre-F) and a stable postfusion conformation (post-F). The pre-F conformation is the primary target for the most potent neutralizing antibodies because it contains unique, highly sensitive epitopes such as Site Ø and Site V [PubMed: 24179220]. Drugs and vaccines targeting the pre-F state, such as nirsevimab and the RSV pre-F vaccines (Arexvy, Abrysvo), work by preventing the protein from undergoing the dramatic conformational change required to fuse the viral and host cell membranes [PubMed: 37018468]. This target is critical for preventing severe lower respiratory tract disease, including bronchiolitis and pneumonia, particularly in high-risk populations like infants and older adults [PubMed: 30726522]. Therapeutic challenges include the potential for viral escape mutations in the antibody-binding sites and the historical risk of vaccine-enhanced respiratory disease, which has been largely mitigated by the use of stabilized prefusion antigens [PubMed: 29439167].

Other names

RSV F proteinFusion glycoproteinRSV pre-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 and blocking membrane fusion.