Neuraminidase of Influenza A virus subtype H5N1 (NA)

Neuraminidase (NA) is a major surface glycoprotein of the Influenza A virus subtype H5N1, existing as a homotetrameric type II transmembrane protein with essential sialidase activity [1, 3]. Its primary biological function is to cleave terminal sialic acid residues from host cell receptors and progeny virions, a process that facilitates the release of new viral particles from infected cells and prevents their aggregation [1, 7]. Beyond viral egress, NA also plays a role in viral entry by cleaving sialic acids within the respiratory mucus layer, allowing the virus to reach target epithelial cells [1, 12]. In the context of H5N1, a highly pathogenic avian influenza strain, NA is a primary target for antiviral drugs known as neuraminidase inhibitors (NAIs), such as oseltamivir and zanamivir [2, 8]. These drugs act as transition-state analogs that bind to the highly conserved active site of the enzyme, effectively blocking its catalytic activity and limiting viral spread [10, 11]. However, the therapeutic utility of NAIs is increasingly challenged by the emergence of drug-resistant mutations, such as the H274Y substitution, which can significantly reduce drug susceptibility while maintaining viral fitness [5, 9].

Other names

SialidaseExo-alpha-sialidaseN1 neuraminidaseN1 NAN1 sialidase

Competitive inhibition of the neuraminidase enzyme by mimicking the transition state of sialic acid hydrolysis, thereby preventing the cleavage of sialic acid residues and blocking the release of progeny virions from infected cells.