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The Respiratory syncytial virus (RSV) fusion (F) glycoprotein is a critical class I viral fusion protein responsible for mediating the entry of the virus into host cells [PubMed: 23559249]. It exists in two primary conformational states: a metastable prefusion (pre-F) form and a stable postfusion (post-F) form [Science, 2013]. The pre-F conformation is the primary target for potent neutralizing antibodies because it displays highly conserved epitopes, such as Site Ø, which are lost upon transition to the post-F state [Nature Communications, 2017]. Subtype B represents one of the two major antigenic lineages of RSV circulating globally, often alternating in dominance with subtype A [Journal of Infectious Diseases, 2020]. Targeting the pre-F conformation of subtype B is essential for broad-spectrum protection in vaccines and monoclonal antibody therapies [NEJM, 2022]. By stabilizing the protein in its prefusion state, therapeutic agents can effectively block the fusion process and prevent infection of the respiratory epithelium [Science, 2019].
Binding to the prefusion conformation of the F protein prevents the structural transition to the postfusion state, thereby inhibiting the fusion of the viral envelope with the host cell membrane and blocking viral entry.
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