Respiratory syncytial virus fusion glycoprotein (prefusion conformation, subgroup B) (RSV Pre-F (Subgroup B))

The Respiratory syncytial virus (RSV) fusion (F) glycoprotein is a class I viral fusion protein essential for the virus to enter host cells (McLellan et al., 2013, Science). It exists in a metastable prefusion (Pre-F) conformation and a stable postfusion (Post-F) conformation. The Pre-F conformation is the primary target for neutralizing antibodies because it contains highly potent epitopes, such as Site Ø, which are lost upon transition to the Post-F state (McLellan et al., 2013). Subgroup B refers to one of the two major antigenic lineages of RSV (A and B), which circulate concurrently and exhibit significant sequence variation in the F protein (Simoes et al., 2022, JID). Targeting the Pre-F protein of subgroup B is critical for broad protection, as mutations in this subgroup have historically led to the failure of some monoclonal antibody candidates like suptavumab (Simoes et al., 2022). Modern vaccines and monoclonal antibodies specifically stabilize or target this prefusion state to prevent the fusion of the viral envelope with the host cell membrane (FDA, Abrysvo Label). By blocking this structural rearrangement, these therapeutics effectively neutralize the virus before it can infect the respiratory epithelium. Clinical management of RSV relies heavily on ensuring that these interventions maintain high affinity for both subgroup A and subgroup B variants (FDA, Beyfortus Label).

Other names

RSV-B F proteinRSV fusion proteinPrefusion F glycoproteinRSV-FRespiratory syncytial virus B fusion proteinRSV F protein

Neutralization of viral infectivity by binding to specific epitopes (e.g., Site Ø or Site V) on the prefusion conformation of the F protein, thereby preventing the structural rearrangement required for fusion of the viral and host cell membranes (McLellan et al., 2013; FDA, Beyfortus Label).