Influenza A virus neuraminidase (subtype N9) (N9 NA)

Influenza A virus neuraminidase (subtype N9) is a major surface glycoprotein and essential enzyme of the H7N9 avian influenza virus, which emerged in 2013 and is characterized by a high case fatality rate in humans [1][16]. As a sialidase, the protein cleaves terminal sialic acid residues from host cell receptors and viral glycoproteins, a process that is vital for the release of progeny virions from infected cells and for preventing viral aggregation at the cell surface [4][17]. Unique to the N9 subtype found in H7N9, the protein also possesses a secondary hemadsorption site that allows it to assist the hemagglutinin (HA) protein in binding to host receptors, potentially enhancing viral fitness and interspecies transmission [4][8]. This enzyme is the primary therapeutic target for neuraminidase inhibitors (NAIs) such as oseltamivir and zanamivir, which competitively bind to the active site to block viral spread [1][5]. However, the H7N9 neuraminidase has demonstrated a concerning propensity for developing resistance-associated mutations, particularly the R292K substitution, which significantly reduces the binding affinity of several clinical inhibitors without compromising the virus's ability to replicate or transmit [2][3]. Understanding the structural and functional nuances of N9 NA is therefore critical for the development of next-generation antivirals and for pandemic preparedness efforts directed at avian-origin influenza viruses [12][15].

Other names

N9 neuraminidaseSialidaseExo-alpha-sialidaseN9 NAH7N9 NA

Competitive inhibition of the neuraminidase enzyme prevents the cleavage of terminal sialic acid residues from host cell receptors and viral glycoproteins, thereby blocking the release and spread of progeny virions from infected cells [1][5].