Influenza A virus H7N9 neuraminidase (NA (N9))

The Influenza A virus H7N9 neuraminidase (NA, N9 subtype) is a tetrameric viral surface glycoprotein enzyme essential for influenza A replication, comprising a cytoplasmic tail, transmembrane domain, stalk, and catalytic head with a conserved active site featuring eight key residues that interact with sialic acid substrates. It cleaves terminal sialic acids from cellular receptors and viral glycoproteins, preventing progeny virion aggregation on infected cells and enabling efficient release and spread to new targets, while also aiding virus entry by clearing mucus barriers and facilitating movement across sialylated surfaces in balance with hemagglutinin (HA). In H7N9 infections, NA contributes to human disease severity, as seen in avian-origin outbreaks, with structural features like the 150-loop creating a secondary sialic acid-binding site that enhances catalytic efficiency. As a major antiviral target, NA is inhibited by licensed drugs such as oseltamivir and zanamivir, which bind its active site to block replication in influenza A and B viruses. However, resistance via mutations like R294K can emerge, though often with reduced viral fitness, highlighting challenges in long-term efficacy. Structural studies of H7N9 NA, including crystal and cryo-EM complexes with antibodies, reveal antigenic sites for broader protection strategies beyond small molecules.

Other names

N9 neuraminidaseinfluenza A virus neuraminidase (N9 subtype)

Competitive inhibition of the active site by sialic acid analogs, preventing sialic acid cleavage and blocking virus release and spread; some form stabilized covalent intermediates for permanent inactivation