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

The Influenza virus neuraminidase secondary sialic acid-binding site (SBS) is a distinct, non-catalytic pocket located on the surface of the neuraminidase (NA) protein, separate from the primary enzymatic active site (Vavricka et al., 2011). While the primary site is responsible for cleaving sialic acid residues to facilitate the release of progeny virions, the SBS serves as an auxiliary binding site that tethers the virus to host cell sialic acid-containing receptors (Uhlendorff et al., 2009). This site is predominantly found in avian influenza strains and certain human pandemic strains, such as H1N1 and H5N1, where it contributes to hemadsorption and enhances the catalytic efficiency of the enzyme by recruiting substrates to the nearby active site (Zhu et al., 2012). In the context of disease, the SBS is a critical determinant of viral fitness and host-range adaptation, as it modulates the balance between hemagglutinin-mediated binding and neuraminidase-mediated release (Du et al., 2021). Although current FDA-approved neuraminidase inhibitors like oseltamivir and zanamivir primarily target the catalytic site, the SBS is an emerging therapeutic target for the development of next-generation antivirals designed to overcome drug resistance. Blocking the SBS can inhibit viral attachment and reduce the overall rate of sialic acid cleavage, providing a synergistic effect when combined with traditional inhibitors (Mok et al., 2013).

Other names

Secondary sialic acid-binding siteHemadsorption siteNon-catalytic sialic acid-binding siteNA secondary siteSialic acid-binding site 2

Inhibition of viral attachment to host sialic acid receptors and reduction of neuraminidase catalytic efficiency by blocking substrate recruitment to the active site.