Respiratory syncytial virus pre-fusion fusion glycoprotein (RSV PreF)

The Respiratory syncytial virus (RSV) pre-fusion fusion (F) glycoprotein is a critical class I viral fusion protein situated on the surface of the RSV virion, where it facilitates viral entry into host respiratory epithelial cells [1, 2]. It is synthesized as an inactive F0 precursor that is cleaved by host proteases into F1 and F2 subunits, which then assemble into a metastable trimeric pre-fusion conformation [2]. Upon contact with the host cell, this pre-fusion protein undergoes a dramatic and irreversible structural rearrangement into a stable post-fusion form, a process that drives the fusion of the viral envelope with the host cell membrane [3, 4]. Most potent neutralizing antibodies produced during natural infection or through vaccination target highly sensitive epitopes, such as Site Ø and Site V, which are exclusively present in the pre-fusion state and are lost when the protein transitions to the post-fusion form [1, 3]. Modern therapeutic strategies, including long-acting monoclonal antibodies like nirsevimab and recently approved vaccines like Arexvy and Abrysvo, specifically target or utilize the stabilized pre-fusion conformation to provide superior protection compared to older post-fusion-based approaches [4, 5]. Clinically, RSV is a leading cause of severe lower respiratory tract infections such as bronchiolitis and pneumonia, making the pre-fusion F protein a high-priority target for global public health efforts [3, 8].

Other names

RSV fusion proteinRSV F glycoproteinPre-fusion F proteinPre-fusion RSV-FFusion glycoprotein F0DS-Cav1RSV-F

Neutralization of viral entry by binding to the metastable pre-fusion conformation of the F glycoprotein and preventing its transition to the stable post-fusion state, thereby blocking the fusion of the viral envelope with the host cell membrane [1, 2, 6].