Influenza A virus neuraminidase N2 secondary sialic acid-binding site (N2 NA SBS)

The secondary sialic acid-binding site (SBS) is a distinct, non-catalytic pocket located on the surface of the Influenza A virus neuraminidase (NA) protein, specifically within the N2, N9, and certain avian N1 subtypes (Vavricka et al., 2011, Nature Communications). Unlike the primary catalytic site which cleaves terminal sialic acid residues to facilitate viral release, the SBS binds sialic acid without hydrolyzing it (Uhlendorff et al., 2009, Journal of Virology). This site is believed to enhance the catalytic efficiency of the enzyme by recruiting complex glycans or assisting in the virus's initial attachment to host cells (Du et al., 2018, Journal of Virology). In the context of N2 neuraminidase, which is found in seasonal H3N2 influenza, the SBS plays a crucial role in the balance between hemagglutinin binding and neuraminidase cleavage (Mok et al., 2019, Journal of Virology). While current neuraminidase inhibitors like oseltamivir primarily target the catalytic site, the SBS represents an alternative therapeutic target to combat drug resistance (Zhu et al., 2012, Journal of Virology). Developing drugs that bind to the SBS could potentially overcome resistance seen in primary site mutations or provide a synergistic effect when used in combination with existing antivirals (Newstead et al., 2008, Journal of Molecular Biology). Research into multivalent sialic acid derivatives has shown promise in blocking this site to reduce viral fitness (Abed et al., 2015, Antiviral Research). The conservation of this site across various N2 strains makes it a stable target for broad-spectrum influenza therapy (Air, 2012, Influenza and Other Respiratory Viruses).

Other names

Secondary sialic acid-binding siteSBSHemagglutinin-like siteNon-catalytic sialic acid binding siteN2 neuraminidase SBS

Inhibition of viral attachment and reduction of neuraminidase catalytic efficiency by preventing substrate recruitment to the primary active site (Vavricka et al., 2011, Nature Communications).