Respiratory syncytial virus fusion protein (RSV F) - post-fusion conformation (RSV F (post-fusion))

The Respiratory syncytial virus (RSV) fusion (F) protein is a Class I viral fusion glycoprotein that is essential for viral entry into host cells [2, 15]. It mediates the fusion of the viral envelope with the host cell membrane and is also responsible for the formation of multinucleated syncytia [7, 19]. The protein exists in two primary conformations: a metastable pre-fusion (pre-F) state and a highly stable post-fusion (post-F) state [2, 16]. The post-fusion conformation represents the final, triggered state of the protein after the fusion process is complete, characterized by a stable six-helix bundle structure [11, 15]. While the pre-fusion form is the target of the most potent neutralizing antibodies, the post-fusion form displays several neutralizing epitopes, including Sites I, II, and IV [9, 13]. Monoclonal antibodies such as Palivizumab target Site II, which is present on both conformations, while others like 131-2a are specific to the post-fusion state [4, 10]. Small molecule inhibitors like Presatovir act by preventing the conformational transition from the pre-fusion to the post-fusion state [3, 20]. Historically, the post-fusion conformation was a primary focus for vaccine development, although it was later found that pre-fusion-stabilized antigens elicit superior neutralizing responses [21, 23]. Targeting this protein is a key strategy for preventing severe lower respiratory tract infections, such as bronchiolitis and pneumonia, in vulnerable populations [2, 17]. Additionally, the F protein has been shown to trigger p53-dependent apoptosis in infected epithelial cells, contributing to airway obstruction and inflammation [19].

Other names

RSV F proteinFusion glycoproteinRSV Fpost-fusion FpostFRSV F1/F2 proteinSynagis target

Neutralization of viral entry and inhibition of membrane fusion by binding to specific antigenic sites (e.g., Site I, II, or IV) or by blocking the conformational transition from the pre-fusion to the post-fusion state [3, 9, 11].