Respiratory syncytial virus and human metapneumovirus prefusion fusion glycoprotein (RSV/hMPV preF)

The Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (hMPV) prefusion fusion (F) glycoproteins are essential Class I viral fusion proteins located on the viral envelope (McLellan et al., Science 2013). These proteins are responsible for mediating the fusion of the viral and host cell membranes, a process triggered by a massive conformational rearrangement from a metastable prefusion state to a highly stable postfusion state (Battles et al., Nature Communications 2017). The prefusion conformation is the primary target for potent neutralizing antibodies because it contains highly sensitive epitopes, such as Site Ø, which are absent in the postfusion form (Graham, Immunological Reviews 2011). RSV and hMPV are leading causes of lower respiratory tract infections globally, particularly in infants and older adults, often resulting in bronchiolitis and pneumonia (NIH, 2023). Therapeutic interventions, including monoclonal antibodies like Nirsevimab and vaccines like Arexvy or mRNA-1365, specifically target the prefusion F protein to block viral entry and provide broad protection against these pneumoviruses (Moderna, 2024).

Other names

RSV F proteinhMPV F proteinPneumovirus fusion proteinPrefusion F glycoproteinRSV preFhMPV preF

Neutralization of viral particles by binding to the prefusion conformation of the F protein, which prevents the structural transition to the postfusion state required for membrane fusion and viral entry into host cells (McLellan et al., Science 2013; StatPearls, 2023).