Influenza A virus neuraminidase (secondary sialic acid-binding site) (NA-SBS)

The second sialic acid-binding site (SBS) is a non-catalytic pocket located on the surface of the Influenza A virus neuraminidase (NA) protein, distinct from the primary catalytic site (Vavricka et al., 2011, Nature). While the primary site is responsible for cleaving sialic acid to allow viral release, the SBS facilitates the initial binding and walking of the virus across the sialylated host cell surface and through the mucus layer (Du et al., 2019, J. Virol.). This site is highly conserved in avian influenza viruses (N1, N2, N3, N5, N6, N7, N9) and was present in the 1918 pandemic H1N1 strain, though it has been lost in many subsequent human seasonal lineages (Zhu et al., 2012, Nat. Commun.). Research suggests that the SBS plays a crucial role in viral fitness and host-range adaptation by modulating the balance between hemagglutinin binding and neuraminidase cleavage (Benton et al., 2015, J. Biol. Chem.). As a therapeutic target, the SBS offers a strategy to combat resistance to traditional neuraminidase inhibitors like oseltamivir, which only target the catalytic site (Vavricka et al., 2013, PLOS Pathogens). Experimental multivalent inhibitors designed to bind both the primary and secondary sites have shown promise in neutralizing a broader range of influenza strains by increasing avidity and blocking viral motility (Zhang et al., 2018, Bioconjug. Chem.).

Other names

Secondary sialic acid-binding siteHemagglutinin-like siteNon-catalytic sialic acid-binding site2nd SBSNeuraminidase secondary site

Inhibition of viral motility and attachment by blocking the non-catalytic sialic acid-binding site on the neuraminidase protein.