alpha2,6-linked sialic acid receptor (alpha2,6-SA)

The alpha2,6-linked sialic acid receptor is the primary host cell attachment factor for human-adapted influenza A viruses, including the H1N1 subtype [Shinya et al., 2006]. These receptors consist of N-acetylneuraminic acid linked to galactose via an alpha2,6-glycosidic bond, a configuration predominantly found in the human upper respiratory tract [Gamblin & Skehel, 2010]. The viral surface protein hemagglutinin (HA) specifically recognizes this linkage to mediate viral entry into host cells through endocytosis [Wiley & Skehel, 1987]. In contrast, avian influenza viruses typically prefer alpha2,3-linked sialic acids, which are more prevalent in the human lower respiratory tract and avian enteric tracts [Matrosovich et al., 2004]. Therapeutic strategies targeting this receptor interaction include the use of recombinant sialidases like DAS181, which enzymatically remove the receptors from the cell surface to prevent viral docking [Malakhov et al., 2006]. Other approaches involve small molecules like Umifenovir or neutralizing antibodies that bind to the HA protein to block its interaction with the sialic acid [Blaising et al., 2014]. Because this interaction is the initial step of infection, it is a critical determinant of host range and viral transmissibility [Long et al., 2019]. Monitoring the binding affinity of emerging H1 strains to these receptors is essential for pandemic preparedness and vaccine development [Stevens et al., 2006].

Other names

Neu5Ac-alpha2,6-GalHuman-type influenza receptorSialic acid-containing glycansN-acetylneuraminic acid receptorHuman sialic acid receptors via influenza A H1 hemagglutinin

The mechanism of action involves the prevention of viral attachment and entry. This is achieved either by the enzymatic removal of the sialic acid receptors from the host cell surface (e.g., DAS181) or by binding to the viral hemagglutinin protein to block its ability to engage with these receptors (e.g., Umifenovir, neutralizing antibodies).