Respiratory syncytial virus fusion protein (pre-fusion trimer) (RSV F (pre-fusion))

The Respiratory syncytial virus (RSV) fusion (F) protein is a critical class I viral fusion glycoprotein located on the viral envelope, responsible for mediating the fusion of the viral and host cell membranes [1, 2]. It is synthesized as an inactive precursor (F0) that is cleaved into F1 and F2 subunits, which then assemble into a metastable pre-fusion trimer [1]. Upon contact with a host cell, the pre-fusion trimer undergoes a massive conformational rearrangement into a highly stable post-fusion state, a process that drives the fusion of the two membranes and allows the viral genome to enter the cytoplasm [2, 5]. The pre-fusion conformation is the most relevant target for therapeutic intervention because it contains the most potent neutralizing epitopes, such as Site Ø and Site V, which are absent in the post-fusion form [2, 5]. Modern vaccines and monoclonal antibodies are specifically designed to stabilize or target this pre-fusion state to elicit a robust immune response and prevent infection [3, 4]. This approach has led to the successful development of preventatives for RSV-associated bronchiolitis and pneumonia in vulnerable populations, including infants and the elderly [3, 4]. Citations: [1] UniProt P03420; [2] McLellan JS, et al. Science. 2013;342(6158):592-598; [3] FDA Label: Arexvy; [4] FDA Label: Beyfortus; [5] Graham BS. Science. 2017;356(6339):713-717.

Other names

RSV F proteinFusion glycoproteinPre-FRSV-FRSV fusion glycoprotein

Binding to the pre-fusion conformation of the F protein to prevent the structural transition to the post-fusion state, thereby inhibiting viral-cell membrane fusion and neutralizing the virus.