Nipah virus fusion glycoprotein F (NiV-F)

The Nipah virus fusion glycoprotein F is a class I viral fusion protein that plays an essential role in the entry of the Nipah virus into host cells [1, 4]. It is synthesized as an inactive precursor, F0, which undergoes proteolytic cleavage by host cell cathepsins in the endosomal compartment to form two disulfide-linked subunits, F1 and F2 [4, 13]. The protein is displayed on the viral envelope as a metastable prefusion trimer [1, 7]. Upon triggering by the attachment glycoprotein (G) following its binding to host receptors ephrin-B2 or ephrin-B3, the F protein undergoes a dramatic and irreversible conformational change into a stable postfusion six-helix bundle [1, 10]. This structural transition drives the fusion of the viral envelope with the host cell membrane, facilitating the release of the viral genome into the cytoplasm [1, 16]. Additionally, the F protein mediates cell-to-cell fusion, leading to the formation of multinucleated syncytia, which is a hallmark of Nipah virus pathogenesis and contributes to tissue damage and viral spread [2, 8]. Due to its critical function and relatively high sequence conservation, the F glycoprotein is a primary target for the development of therapeutic monoclonal antibodies and vaccines [13, 14]. Current research focuses on stabilizing the prefusion conformation to elicit potent neutralizing antibody responses [1, 14]. Experimental therapies include monoclonal antibodies like mAb66 and fusion-inhibitory peptides that block the conformational transition required for membrane fusion [1, 16].

Other names

Fusion glycoprotein F0Protein FNiV-FNipah virus F proteinFusion protein

Neutralization of viral entry by stabilizing the prefusion conformation of the F protein or blocking the transition to the postfusion six-helix bundle, thereby preventing membrane fusion [1, 16].