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The Respiratory syncytial virus subtype A fusion (F) protein in its prefusion conformation is a critical viral surface glycoprotein responsible for mediating the fusion of the viral envelope with the host cell membrane [7, 13]. It is a class I viral fusion protein that exists in a metastable prefusion state (PreF) before undergoing a dramatic structural rearrangement into a highly stable postfusion state (PostF) to facilitate viral entry [1, 3]. This prefusion form is the primary target for potent neutralizing antibodies, as it displays highly sensitive epitopes, such as site Ø and site V, which are lost upon transition to the postfusion state [5, 6]. In the context of disease, RSV is a leading cause of severe lower respiratory tract infections, including bronchiolitis and pneumonia, particularly in infants, the elderly, and immunocompromised individuals [2, 19]. Therapeutic strategies targeting the prefusion F protein include stabilized subunit vaccines, mRNA vaccines, and long-acting monoclonal antibodies [4, 10, 11]. These interventions work by inducing or providing antibodies that bind to the prefusion protein, thereby locking it in its inactive state or sterically hindering its interaction with host cells, effectively preventing infection and reducing disease severity [9, 15].
Neutralization of viral entry by binding to and stabilizing the prefusion conformation of the F protein, thereby preventing the structural transition to the postfusion state required for membrane fusion [9, 16].
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