Respiratory syncytial virus fusion protein heptad repeat B pocket (RSV F HRB pocket)

The Respiratory syncytial virus (RSV) fusion (F) protein is a Class I viral fusion protein essential for the entry of the virus into host cells by mediating the fusion of the viral envelope with the host cell membrane. It exists as a metastable prefusion trimer that, upon triggering, undergoes a massive conformational rearrangement into a stable postfusion state, characterized by the formation of a six-helix bundle (6HB) where three C-terminal heptad repeat B (HRB) helices pack into the grooves of a central N-terminal heptad repeat A (HRA) coiled-coil. The heptad repeat B pocket refers to a hydrophobic cavity within the central core of the prefusion F protein trimer, involving residues from the HRB region and the fusion peptide. This pocket is a critical therapeutic target for small-molecule fusion inhibitors, such as presatovir and ziresovir, which bind to this site to stabilize the prefusion conformation and prevent the structural transition required for membrane fusion. Targeting this pocket effectively blocks viral infection and the formation of syncytia, making it a primary focus for the development of RSV antivirals.

Other names

RSV F protein central cavityRSV F protein fusion inhibitor binding pocketRSV F protein HRB-binding siteRespiratory syncytial virus fusion glycoproteinRSV F1 subunit heptad repeat B pocket

Small-molecule fusion inhibitors bind to the central cavity (HRB pocket) of the prefusion RSV F protein trimer, stabilizing the metastable prefusion conformation and preventing the structural rearrangement into the postfusion six-helix bundle (6HB), thereby blocking viral-host membrane fusion.