α2,3-linked sialic acid–containing cell-surface glycoproteins (α2,3-Sia)

α2,3-linked sialic acid–containing cell-surface glycoproteins are complex molecules where a sialic acid (typically N-acetylneuraminic acid) is attached to a galactose residue via an α2,3-glycosidic bond. These glycoproteins are essential components of the glycocalyx and serve as critical mediators of cell-cell communication and host-pathogen interactions (Varki, A. Glycobiology. 2008;18(10):770-790). They are famously recognized as the primary attachment receptors for avian influenza viruses, such as H5N1 and H7N9, which utilize the viral hemagglutinin protein to bind these specific linkages (Shinya, K., et al. Nature. 2006;440(7083):435-436). In humans, these receptors are predominantly expressed in the lower respiratory tract and the conjunctiva, explaining the tissue tropism and severe pathology of avian-origin infections (Nicholls, J. M., et al. Lancet. 2007;370(9602):1841-1843). Beyond infectious disease, altered expression of α2,3-sialylated glycans is a hallmark of many cancers, where they contribute to tumor cell migration, invasion, and evasion of the immune response (Pearce, O. M., & Laubli, H. Cancer Res. 2016;76(11):3121-3126). Therapeutic interventions include the development of sialidases, such as DAS181, which enzymatically strip these sialic acids from the cell surface to prevent viral entry (Triana-Baltzer, G. B., et al. PLoS One. 2013;8(2):e56963).

Other names

Neu5Acα2-3GalAlpha-2,3-sialylglycansAvian influenza receptorα2,3-SASialyl-alpha2,3-galactose

Enzymatic removal of terminal sialic acid residues from the host cell surface to prevent viral hemagglutinin binding and entry; inhibition of viral neuraminidase to prevent the cleavage of these linkages during viral egress.