Heparan sulfate proteoglycans and N-linked sialic acid-containing glycans (HSPG/Sialic acid glycans)

Heparan sulfate proteoglycans (HSPGs) and N-linked sialic acid-containing glycans are complex carbohydrate-containing molecules located on the surface of almost all mammalian cells. HSPGs consist of a core protein with attached heparan sulfate glycosaminoglycan chains, while N-linked sialic acid glycans are oligosaccharides attached to proteins via asparagine residues, ending in sialic acid. These molecules serve as critical attachment receptors or co-receptors for a wide variety of viruses, including Influenza, SARS-CoV-2, and Adeno-associated viruses (AAV), by facilitating the initial docking of the pathogen to the host cell. Beyond viral entry, they play fundamental roles in cell-cell signaling, basement membrane integrity, and the regulation of growth factor activity. Therapeutic targeting of these glycans involves the use of mimetics to competitively inhibit viral binding or enzymes like sialidases to remove the glycan receptors from the cell surface. However, due to their ubiquitous nature and essential roles in physiology, drugs targeting these molecules must be carefully designed to avoid interfering with normal cellular processes such as blood coagulation and tissue repair.

Other names

HSPGsSialylated glycansViral attachment receptorsCell surface glycocalyx components

Viral entry inhibition, Competitive binding to attachment factors, Enzymatic cleavage of cell surface glycans