α2-6-linked sialic acid-containing glycans (α2-6-SiA)

α2-6-linked sialic acid-containing glycans are terminal carbohydrate structures found on the surface glycoproteins and glycolipids of human respiratory epithelial cells (Shinya et al., 2006, Nature). These glycans are characterized by an N-acetylneuraminic acid (Neu5Ac) residue attached to a galactose residue via an α2-6 glycosidic linkage, a configuration that is predominantly expressed in the human upper respiratory tract, including the nose, soft palate, and trachea (Nicholls et al., 2007). They serve as the primary host cell receptors for human-adapted influenza A and B viruses; the viral hemagglutinin (HA) protein specifically recognizes and binds to these α2-6 linkages to initiate cell entry (Kumlin et al., 2008). In contrast, avian influenza viruses typically prefer α2-3-linked sialic acids, making the α2-6 linkage a critical determinant of human-to-human transmissibility and host range. Therapeutically, these glycans are targeted by sialidases such as DAS181 (Fludase), a recombinant fusion protein that enzymatically removes the terminal sialic acids, thereby "de-receptoralizing" the respiratory epithelium and blocking viral infection (Malakhov et al., 2006). While neuraminidase inhibitors like oseltamivir do not bind the glycans directly, they prevent the virus from detaching from these receptors during the budding phase of the viral life cycle.

Other names

Neu5Acα2-6Gal6'-sialyllactose-containing glycansHuman-type influenza receptorsAlpha 2-6 sialic acidsSiaα2-6Gal

Enzymatic cleavage of terminal sialic acid residues from the host cell surface to prevent viral hemagglutinin binding and subsequent viral entry.