Respiratory syncytial virus fusion glycoprotein F (RSV F) (RSV F)

The Respiratory syncytial virus (RSV) fusion glycoprotein F is a Class I viral fusion protein essential for the entry of the virus into host cells (UniProt P03420). It undergoes a dramatic conformational change from a metastable pre-fusion state to a stable post-fusion state, a process that drives the fusion of the viral envelope with the host cell membrane (Battles and McLellan, 2019 [PMID: 30944447]). A key step in this transition is the assembly of the six-helix bundle (6HB), formed by the interaction of three Heptad Repeat 1 (HR1) domains and three Heptad Repeat 2 (HR2) domains. This HR1/HR2 interface is a critical site for therapeutic intervention, as small molecule fusion inhibitors and peptide mimetics can bind to the HR1 hydrophobic grooves (Mackman et al., 2015 [PMID: 25372214]). By binding to these grooves, these agents prevent the docking of HR2 and effectively halt the fusion process before the viral and cellular membranes can merge. Targeting this interface is a validated strategy for developing antivirals to treat RSV-induced bronchiolitis and pneumonia, particularly in high-risk populations like infants and the elderly (Zhao et al., 2022 [PMID: 35417614]). Unlike monoclonal antibodies that often target the pre-fusion apex, small molecule inhibitors targeting the HR1/HR2 bundle provide a distinct pharmacological approach to blocking viral entry. Clinical candidates like Ziresavir and Presatovir have demonstrated the potential of this target to reduce viral load and clinical symptoms in human trials.

Other names

RSV FFusion proteinRSV fusion glycoproteinRSV-FF protein

Inhibition of viral-cell membrane fusion by binding to the HR1 triple helix and preventing the formation of the six-helix bundle (6HB) [PMID: 25372214, PMID: 30944447].