Respiratory syncytial virus fusion glycoprotein (pre-fusion conformation) (RSV pre-F)

The Respiratory syncytial virus (RSV) fusion (F) glycoprotein is a Class I viral fusion protein that is essential for viral entry into host cells by mediating the fusion of the viral and cellular membranes [1]. It is synthesized as an inactive precursor, F0, which is cleaved into F1 and F2 subunits that form a metastable pre-fusion (pre-F) trimer [4]. Upon triggering, the pre-F protein undergoes a massive conformational rearrangement into a highly stable post-fusion (post-F) state, a process that facilitates membrane merging [1, 2]. The pre-fusion conformation is the primary target for potent neutralizing antibodies because it displays unique antigenic sites, such as Site Ø and Site V, which are not present on the post-fusion form [1]. Antigenic Site II is another major target found on both conformations and is the binding site for the monoclonal antibody palivizumab [3]. Modern therapeutic approaches, including the monoclonal antibody nirsevimab and stabilized pre-F vaccines like Arexvy and Abrysvo, specifically target the pre-fusion state to provide high levels of protection against RSV-related lower respiratory tract disease [3, 5]. Citations: [1] McLellan JS, et al. Science. 2013;340(6136):1113-7. [2] Graham BS. Immunol Rev. 2017;239(1):149-166. [3] FDA. Beyfortus (nirsevimab) Prescribing Information. 2023. [4] UniProt. P03420 (F_RSVA4). [5] Papi A, et al. N Engl J Med. 2023;388(7):595-608.

Other names

RSV F proteinRespiratory syncytial virus fusion proteinRSV-FFusion glycoprotein F0RSV pre-fusion FRSV F1/F2 subunits

Monoclonal antibodies and vaccines target the RSV fusion glycoprotein to neutralize the virus. Antibodies bind to specific antigenic sites (such as Site II, Site Ø, or Site V) on the pre-fusion conformation, preventing the structural transition to the post-fusion state and thereby blocking the fusion of the viral envelope with the host cell membrane [1, 3].