Influenza A virus H9N2 neuraminidase (NA) (NA)

Influenza A virus H9N2 neuraminidase (NA) is a critical surface glycoprotein and enzyme found on the H9N2 subtype of the influenza A virus [NIH, 2021; Acta Naturae, 2012]. It functions as an exosialidase (EC 3.2.1.18), catalyzing the cleavage of terminal sialic acid residues from host cell receptors and viral glycoproteins [NIH, 2021]. This enzymatic activity is essential for the release of newly formed virions from the surface of infected cells, preventing their aggregation and facilitating the spread of the virus throughout the respiratory tract [NIH, 2021; MDPI, 2020]. Additionally, NA helps the virus penetrate the mucus layer of the respiratory tract by cleaving sialic acids on mucins, which promotes the infection of new target cells [NIH, 2021]. H9N2 is a low-pathogenic avian influenza virus that is widespread in poultry and has demonstrated the ability to infect humans, posing a significant public health threat due to its pandemic potential [NIH, 2021; IVAMI, 2023]. Neuraminidase is the primary target for antiviral drugs known as neuraminidase inhibitors (NAIs), such as oseltamivir, zanamivir, and peramivir, which competitively bind to the enzyme's active site and block its function [NIH, 2021; Wikipedia, 2023]. However, the emergence of drug-resistant mutations, such as R292K and E119V, remains a major challenge in the clinical management of influenza infections [ResearchGate, 2019; NIH, 2008].

Other names

NeuraminidaseSialidaseNAH9N2 NAN2 neuraminidaseExosialidase

Neuraminidase inhibitors (NAIs) function as competitive inhibitors that target the highly conserved active site of the viral neuraminidase enzyme. By mimicking the oxocabenium ion transition state of the sialic acid cleavage reaction, these drugs bind with high affinity to the enzyme, preventing it from removing terminal sialic acid residues from host cell receptors and viral glycoproteins. This inhibition blocks the release of newly synthesized virions from the surface of infected cells and causes them to aggregate, thereby limiting the spread of the infection to adjacent cells and throughout the respiratory tract [NIH, 2021; Wikipedia, 2023].