Host glycosaminoglycans (GAGs)

Host glycosaminoglycans (GAGs) are a family of highly negatively charged, linear polysaccharides composed of repeating disaccharide units, primarily located on cell surfaces and within the extracellular matrix (ECM) [1]. They include diverse molecules such as heparan sulfate, chondroitin sulfate, and hyaluronic acid, which are essential for maintaining tissue structural integrity and regulating physiological processes like blood coagulation, wound healing, and cell signaling [1]. In the context of infectious disease, many pathogens—including viruses like SARS-CoV-2 and various bacteria—exploit host GAGs as initial attachment receptors to facilitate cell entry and infection [2]. Furthermore, GAGs are implicated in cancer progression and inflammation by modulating the activity of growth factors and chemokines [1]. Pharmacologically, GAGs like heparin are widely used as clinical anticoagulants, while GAG mimetics are being developed to block viral attachment or inhibit tumor metastasis [3]. However, the therapeutic use of GAG-targeting agents is often complicated by risks such as hemorrhage and heparin-induced thrombocytopenia due to their broad biological activity [3]. Sources: [1] Varki A, et al. Essentials of Glycobiology. 3rd edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2015-2017. [2] Clausen TM, et al. SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2. Cell. 2020;183(4):1043-1057. [3] StatPearls [Internet]. Heparin. Treasure Island (FL): StatPearls Publishing; 2023. [4] Muenzer J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr. 2004;144(5 Suppl):S27-34.

Other names

MucopolysaccharidesAcidic heteropolysaccharidesGlycosaminoglycan chainsHost GAGs

Drugs targeting host glycosaminoglycans typically act by mimicking their structure to competitively inhibit pathogen binding, neutralizing their negative charge to reverse anticoagulant effects, or utilizing them as enzymatic co-factors to accelerate the inhibition of serine proteases in the coagulation cascade.