Influenza virus neuraminidase (NA) (NA)

Influenza virus neuraminidase (NA) is a critical surface glycoprotein and essential enzyme found on the envelope of influenza A and B viruses [2, 5]. It functions as an exo-sialidase (EC 3.2.1.18), specifically cleaving terminal sialic acid residues from host cell receptors and nascent viral glycoproteins [2, 9]. This enzymatic activity is crucial during the final stages of the viral life cycle, as it facilitates the release of progeny virions from the infected cell surface and prevents their aggregation [1, 3]. Beyond viral release, NA also aids in the penetration of the respiratory mucus layer by degrading sialic acid-containing mucins, thereby allowing the virus to reach target epithelial cells [2, 8]. As a primary therapeutic target, NA is inhibited by a class of drugs known as neuraminidase inhibitors (NAIs), including oseltamivir, zanamivir, and peramivir [7, 12]. These drugs competitively bind to the highly conserved active site of the enzyme, mimicking the transition state of sialic acid and preventing substrate cleavage [1, 9]. While highly effective in reducing the duration and severity of influenza, the clinical utility of NAIs is challenged by the emergence of drug-resistant mutations, such as the H275Y substitution in the N1 subtype [10, 14]. Consequently, NA remains a focal point for global surveillance and the development of novel antiviral strategies and vaccines [15, 16].

Other names

SialidaseExo-alpha-sialidaseAcetylneuraminyl hydrolaseViral neuraminidaseN-acetylneuraminate glycohydrolase

Neuraminidase inhibitors (NAIs) are transition-state analogues that competitively bind to the highly conserved active site of the neuraminidase enzyme [1, 7]. By mimicking the oxocarbonium ion transition state of sialic acid, these drugs block the enzyme's ability to cleave terminal sialic acid residues from host cell receptors and viral glycoproteins [3, 9]. This prevents the release of newly formed progeny virions from the infected cell surface, leading to viral aggregation and limiting the spread of infection to adjacent cells [1, 5].