Neuraminidase (H5N1 influenza virus) (NA)

Neuraminidase (NA) is a critical surface glycoprotein of the highly pathogenic avian influenza A (H5N1) virus, structured as a mushroom-shaped homotetramer [3, 16]. It functions as an exosialidase (EC 3.2.1.18) that catalyzes the cleavage of terminal sialic acid residues from host cell glycoconjugates and viral glycoproteins [4, 16]. This enzymatic process is vital for the release of newly formed virions from the host cell membrane, preventing their aggregation and facilitating their spread throughout the respiratory tract and other tissues [1, 15, 16]. Additionally, NA aids viral movement through the respiratory mucus layer by degrading decoy receptors [15, 16]. As a primary target for antiviral therapy, NA is inhibited by drugs such as oseltamivir and zanamivir, which block the enzyme's active site to trap progeny viruses at the cell surface [1, 14, 17]. However, the therapeutic utility of these drugs is often challenged by the emergence of resistance-conferring mutations, most notably the H274Y substitution in the N1 subtype [1, 5, 14]. The balance between NA's sialidase activity and the hemagglutinin's (HA) receptor binding activity is crucial for viral fitness and adaptation to mammalian hosts [13, 15].

Other names

SialidaseN1 neuraminidaseExosialidaseAcylneuraminyl hydrolaseNRAMEC 3.2.1.18

The enzyme cleaves alpha-ketosidic linkages between terminal sialic acid and adjacent sugar residues on the host cell surface and viral envelope [16]. Neuraminidase inhibitors (NAIs) bind to the enzyme's active site, competitively inhibiting this cleavage, which traps progeny virions at the cell membrane and prevents the spread of the infection to new host cells [1, 3, 5, 14].