Fusion glycoprotein of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) (F protein (RSV F, hMPV F))

The fusion glycoprotein (F protein) of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) is a class I viral fusion protein essential for the entry of these viruses into host cells. It mediates the fusion of the viral envelope with the host cell membrane, enabling infection of airway epithelial cells. The F protein assembles as a homotrimer on the viral surface, undergoing major conformational changes from prefusion to postfusion states during membrane fusion. It is highly conserved within RSV and hMPV families, making it a primary target for vaccines, monoclonal antibodies, and small-molecule antivirals. Neutralizing antibodies typically target the prefusion conformation, and two FDA-approved RSV vaccines (as of 2023) employ stabilized prefusion F antigens. Peptide inhibitors mimicking key F protein domains can block hairpin formation required for fusion. Structural studies have elucidated key neutralizing epitopes for rational vaccine design, and antibody-based prophylaxis (such as nirsevimab) is now in clinical use. The F protein has been successfully engineered for improved vaccine efficacy by stabilizing the prefusion form, resulting in enhanced immunogenicity and safety.

Other names

RSV F proteinhMPV F proteinViral fusion proteinFusion (F) glycoprotein

Neutralizing antibodies bind to epitopes on prefusion and postfusion F glycoprotein, blocking membrane fusion, inhibiting viral entry. Peptide inhibitors block trimer-of-hairpins formation to inhibit fusion. Drugs stabilizing the prefusion conformation prevent fusion activation.