Fusion glycoprotein F of respiratory syncytial virus, prefusion conformation (RSV F (prefusion))

The fusion glycoprotein F of respiratory syncytial virus (RSV), in its prefusion conformation, is a trimeric class I viral fusion protein embedded in the viral envelope[8][9]. Its primary role is to mediate the fusion of the viral and host cell membranes, which is required for viral entry and infection[1][4][9]. The prefusion form (preF) is metastable and present on the viral surface before entry, where its structure exposes unique antigenic sites—such as site Ø and site V—that are the principal targets of highly potent neutralizing antibodies obtained during natural infection or upon vaccination[4][9]. Stabilizing the prefusion form has been key for recent advances in RSV vaccine and antibody development, as it emits much stronger and more protective antibody responses compared to the postfusion form[2][4][9]. The F protein is first synthesized as an inactive precursor (F0), which is then cleaved by host cell proteases into disulfide-linked subunits, F1 and F2, becoming fusion-competent only in the prefusion conformation[7]. Once triggered, the protein undergoes a large conformational change, exposing the hydrophobic fusion peptide, and drives membrane fusion and viral entry[1][9]. As the major target of antiviral drugs, neutralizing antibodies, and vaccines, prefusion F is the principal antigen of interest for RSV immunization and monoclonal antibody therapies[1][4][9][10].

Other names

RSV F protein (prefusion)Respiratory syncytial virus F protein (preF)Viral fusion protein F (prefusion)RSV fusion glycoprotein F (prefusion)RSV preF

Neutralizing antibody binding blocks conformational change required for membrane fusion, thereby preventing viral entry[4][9]. Antibody binding stabilizes prefusion conformation, preventing exposure of the fusion peptide and halting the infection process[9].