Terminal sialic acid residues on respiratory epithelial glycoconjugates (Sia)

Terminal sialic acids are acidic monosaccharides located at the distal ends of glycan chains on the surface of respiratory epithelial cells. These residues are critical components of the glycocalyx and play essential roles in maintaining the physical properties of mucus and mediating cell-cell recognition and signaling (Varki, 2008). In the context of infectious disease, they serve as the primary attachment receptors for various respiratory pathogens, most notably the influenza virus, which binds to these sugars via its hemagglutinin protein to initiate infection (Byrd-Leotis et al., 2017). The specific chemical linkage of the sialic acid—typically alpha 2,3 or alpha 2,6—determines the tissue tropism and host specificity of the virus (Shinya et al., 2006). Therapeutic strategies such as the drug candidate DAS181 (Fludase) utilize recombinant sialidases to enzymatically remove these terminal residues, effectively stripping the host cells of the docking stations required for viral entry. This approach provides a broad-spectrum mechanism to prevent infection by multiple strains of influenza and other sialic acid-dependent viruses.

Other names

Sialic acidN-acetylneuraminic acidNeu5AcSialyl-glycansInfluenza virus receptorHost cell sialic acid

Enzymatic cleavage of terminal sialic acid residues from host cell surface glycoconjugates to remove viral binding sites (Malakhov et al., 2006), or inhibition of viral neuraminidase to prevent the release of progeny virions from these residues (Gubareva et al., 2000).