Respiratory syncytial virus fusion protein (RSV F) (RSV F)

The Respiratory Syncytial Virus (RSV) fusion (F) protein is a class I viral fusion glycoprotein that is essential for the virus to enter host cells by mediating the fusion of the viral and cellular membranes (UniProt P03420). It exists in a metastable prefusion conformation on the surface of the virion and must undergo a dramatic, irreversible structural rearrangement into a highly stable postfusion state to facilitate membrane fusion. The central cavity of the prefusion trimer is a distinct, hydrophobic pocket formed by the assembly of three F1 subunits. This cavity has been identified as a key target for small-molecule fusion inhibitors, which bind and stabilize the prefusion state, thereby preventing the conformational change required for infection (Battles et al., 2016). Drugs targeting this site, such as ziresovir and sisunatovir, are designed to treat active RSV infections, which are a major cause of severe respiratory illness, including bronchiolitis and pneumonia, in infants and the elderly (Cockerill et al., 2021). Unlike monoclonal antibodies that target surface epitopes, these small molecules occupy the internal core of the protein to block its mechanical function.

Other names

RSV F proteinFusion glycoproteinRSV prefusion FPre-FRSV-FPrefusion trimer central cavity

Small molecule inhibitors bind to the central cavity of the prefusion RSV F trimer, stabilizing this metastable state and preventing the conformational rearrangement into the postfusion state, thereby blocking viral-host membrane fusion (Battles et al., 2016; Zheng et al., 2019).