Terminal sialic acid residues on host glycoconjugates (Sia)

Terminal sialic acid residues are nine-carbon acidic monosaccharides typically found at the distal ends of glycan chains on cell surface glycoproteins and glycolipids (Varki, 2008, PMID: 18691683). They play a fundamental role in biological recognition, acting as ligands for various receptors such as Siglecs (Sialic acid-binding immunoglobulin-type lectins), which modulate immune cell activity and maintain self-tolerance (Schauer, 2009, PMID: 19217282). In infectious diseases, these residues serve as the primary attachment points for pathogens like influenza viruses, which utilize their hemagglutinin protein to bind specific sialic acid linkages (e.g., alpha-2,3 or alpha-2,6) on host cells. Cancer cells often exhibit hypersialylation, a process that facilitates immune evasion by engaging inhibitory Siglecs on natural killer cells and macrophages, thereby dampening the anti-tumor response (Pearce and Läubli, 2016, PMID: 27130218). Therapeutic strategies targeting these residues include neuraminidase inhibitors (e.g., oseltamivir) that block the release of viral progeny by preventing the cleavage of these sugars. Additionally, recombinant sialidases like DAS181 (Fludase) are designed to enzymatically strip these terminal sugars from the respiratory epithelium to prevent viral entry (Triana-Alba et al., 2021, PMID: 33556117). Emerging therapies also focus on blocking the interaction between tumor-associated sialic acids and immune cell Siglecs to restore anti-cancer immunity.

Other names

Sialic acidsN-acetylneuraminic acidNeu5AcSialylated glycansSialyl-Lewis XSialyl-Lewis AN-glycolylneuraminic acidNeu5Gc

Enzymatic depletion of terminal sialic acids from the host cell surface to prevent viral entry, or inhibition of viral enzymes (neuraminidases) that cleave these residues to facilitate viral release.