Influenza A virus neuraminidase N9 secondary sialic acid binding site (N9 NA SBS)

The secondary sialic acid binding site (SBS) of N9 neuraminidase is a distinct, non-catalytic pocket located on the surface of the influenza virus neuraminidase (NA) protein, separate from the primary active site (Varghese et al., 1997, Nature). While the primary catalytic site is responsible for cleaving sialic acid to facilitate the release of progeny virions, the SBS in N9 binds sialic acid without cleaving it, which is thought to assist the virus in rolling across the host cell surface to find optimal cleavage sites (Air, 2012, Influenza and Other Respiratory Viruses). In avian-origin N9 strains, this site is particularly well-developed and can even mediate hemagglutination, a function typically associated with the hemagglutinin protein (Zhu et al., 2012, Nature). The SBS plays a significant role in the catalytic efficiency of the enzyme against complex, multivalent substrates found on the cell surface (Vavricka et al., 2011, Journal of Molecular Biology). Although current clinical neuraminidase inhibitors like oseltamivir and zanamivir are designed to target the catalytic site, the SBS has emerged as a strategic target for next-generation antivirals, including multivalent sialic acid conjugates, to overcome drug resistance and enhance inhibitory potency (Du et al., 2018, Journal of Medicinal Chemistry). Blocking this site can prevent viral attachment and reduce the overall fitness of the virus, making it a valuable focus for therapeutic intervention.

Other names

Secondary sialic acid-binding site2nd SBSHemagglutinin-like siteNon-catalytic sialic acid binding site

Inhibition of the neuraminidase enzyme's catalytic activity and prevention of non-catalytic viral attachment or rolling by blocking the secondary sialic acid binding site.