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Influenza A virus neuraminidase (NA) of the N2 subtype is a critical surface glycoprotein and enzyme essential for the viral life cycle (Britannica, 2026; NIH, 2016). It functions as a sialidase, cleaving terminal sialic acid residues from host cell receptors and viral glycoproteins to facilitate the release of newly formed virions from infected cells and prevent their aggregation (NIH, 2016; MDPI, 2023). Beyond viral egress, N2 neuraminidase also aids in viral entry by degrading sialic acids in the respiratory mucus, allowing the virus to reach target epithelial cells (NIH, 2016). This enzyme is the primary target for neuraminidase inhibitors (NAIs) such as oseltamivir and zanamivir, which competitively bind to the highly conserved active site to block viral spread (NIH, 2012; PLOS, 2023). However, the therapeutic utility of these drugs is challenged by the emergence of specific resistance mutations, such as E119V and R292K, which alter the drug-binding pocket (NIH, 2003; WHO, 2024). Monitoring these mutations and viral susceptibility via enzymatic assays is crucial for managing seasonal influenza outbreaks, particularly those caused by H3N2 strains (NIH, 2003; Wikipedia, 2024).
Competitive inhibition of the neuraminidase active site, preventing the cleavage of sialic acid and the release of progeny virions (NIH, 2012; PLOS, 2023).
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