Heparan sulfate and sialic acid-containing host surface polyanions

Heparan sulfate and sialic acid-containing host surface polyanions are essential components of the cellular glycocalyx that serve as primary attachment sites for a diverse range of human pathogens. Heparan sulfate (HS) is a highly sulfated glycosaminoglycan that acts as a critical co-receptor for viruses such as SARS-CoV-2, Herpes Simplex Virus (HSV), and Human Immunodeficiency Virus (HIV) by facilitating initial electrostatic docking (Clausen et al., Cell, 2020; NIH, 2021). Sialic acids (SA) are terminal sugar residues on glycoproteins and glycolipids that are specifically recognized by the hemagglutinin of influenza viruses and other paramyxoviruses to initiate cell entry (Skehel & Wiley, Annu Rev Biochem, 2000). These polyanions are characterized by their dense negative charge, which allows them to interact with basic amino acid clusters on viral surface proteins. Therapeutic strategies targeting these molecules include the use of polyanionic mimetics like suramin or heparin to act as decoy receptors, or enzymatic agents like DAS181 that cleave sialic acid residues to render cells resistant to infection (Witvrouw & De Clercq, Gen Pharmacol, 1997; Belser et al., J Infect Dis, 2007). While effective as broad-spectrum entry inhibitors, these targets present challenges due to their ubiquitous physiological roles in coagulation, inflammation, and growth factor regulation.

Other names

Cell surface polyanionsGlycosaminoglycans and sialylated glycansHost cell attachment factorsHSPGs and sialic acidsGlycocalyx polyanions

Competitive inhibition of pathogen binding to host cells by mimicking the electrostatic properties of surface polyanions or enzymatic depletion of specific glycan residues to prevent viral docking.