Human airway epithelial cell surface sialic acid receptors (SA receptors)

Human airway epithelial cell surface sialic acid receptors are terminal monosaccharides, typically N-acetylneuraminic acid (Neu5Ac), located on the glycans of cell surface glycoproteins and glycolipids (Varki, Glycobiology, 2008). These receptors serve as the primary attachment points for numerous respiratory viruses, including influenza A and B, parainfluenza, and certain coronaviruses (Shinya et al., Nature, 2006). The specificity of viral binding is determined by the linkage between the sialic acid and the underlying galactose residue, with alpha-2,6-linkages predominating in the human upper respiratory tract and alpha-2,3-linkages in the lower respiratory tract (Nicholls et al., The Lancet, 2007). Beyond their role in pathogenesis, these receptors are vital for maintaining the structural integrity of the glycocalyx and modulating cell-cell interactions and immune signaling. Therapeutic interventions like DAS181 (Fludase) target these receptors by enzymatically cleaving them from the cell surface, thereby creating a temporary host-directed barrier against viral entry (Malakhov et al., Antimicrobial Agents and Chemotherapy, 2006). This approach is particularly valuable as a broad-spectrum antiviral strategy that is less susceptible to viral resistance compared to drugs targeting viral proteins. However, the removal of these sugars can potentially impact normal physiological functions, such as mucus clearance and inflammatory responses. Consequently, these receptors are a focal point for research into viral tropism, pandemic preparedness, and the development of novel respiratory therapies (Triana-Falo et al., ACS Central Science, 2022).

Other names

Alpha-2,6-linked sialic acidAlpha-2,3-linked sialic acidN-acetylneuraminic acid receptorsNeu5Ac receptorsInfluenza virus host receptors

Enzymatic desialylation of the host cell surface to deplete the available binding sites for viral hemagglutinin, thereby preventing viral attachment and entry.