Respiratory syncytial virus pre-fusion fusion protein (RSV PreF)

The Respiratory syncytial virus (RSV) pre-fusion fusion protein is the metastable, high-energy conformation of the RSV F glycoprotein that is essential for viral entry into host cells [2, 6]. As a class I viral fusion protein, it facilitates the fusion of the viral envelope with the host cell membrane by undergoing a dramatic and irreversible structural rearrangement into a stable post-fusion state [9, 10]. This conformational change is triggered upon attachment, allowing the viral genome to enter the host cytoplasm and initiate infection [13, 15]. RSV PreF is the primary target for modern prophylactic and therapeutic interventions because it displays highly potent neutralizing epitopes, most notably 'Site Ø' (Site Zero), which are absent in the post-fusion form [2, 25]. Vaccines such as Arexvy and Abrysvo utilize stabilized versions of this pre-fusion protein to elicit a superior immune response compared to earlier post-fusion-based candidates [8, 27]. Additionally, long-acting monoclonal antibodies like Nirsevimab target this conformation to prevent the viral fusion process and protect vulnerable populations from severe respiratory distress [2, 9]. By inhibiting the structural transition or blocking key antigenic sites, these drugs effectively mitigate the risk of bronchiolitis and pneumonia associated with RSV infection [18, 20].

Other names

RSV F proteinRespiratory syncytial virus fusion glycoproteinPre-fusion F proteinMetastable RSV F proteinRSV PreFFusion glycoprotein F0

Neutralization of viral particles and inhibition of membrane fusion by stabilizing the metastable pre-fusion conformation or binding to epitopes specific to the pre-fusion state to block structural rearrangement [2, 10, 12].