Host cell surface polyanion (HSPG/GAG)

Host cell surface polyanions are a diverse group of negatively charged macromolecules, primarily comprising glycosaminoglycans (GAGs) such as heparan sulfate, chondroitin sulfate, and sialic acids, which are covalently attached to proteins on the plasma membrane (Cagno et al., 2019, PubMed). These molecules serve as critical physiological regulators, mediating cell-cell communication, extracellular matrix stability, and the sequestration of various growth factors and cytokines (Kamhi et al., 2013, PubMed). In the context of infectious diseases, many pathogens, including SARS-CoV-2, HIV-1, and Herpes Simplex Virus, exploit these polyanions as initial attachment factors to concentrate on the cell surface before engaging specific entry receptors (Clausen et al., 2020, Cell; Lortat-Jacob, 2009, PubMed). Consequently, they are significant targets for the development of entry inhibitors, which often utilize polyanionic mimics to competitively block pathogen binding (Pirrone et al., 2011, PubMed). Beyond infection, these polyanions play roles in cancer progression by facilitating angiogenesis and tumor cell metastasis, making them targets for enzymatic inhibitors like heparanase antagonists (Vlodavsky et al., 2012, PubMed).

Other names

Cell surface glycosaminoglycansHeparan sulfate proteoglycansSialic acidsSulfated polysaccharidesPolyanionic glycansSurface-associated polyanions

Competitive inhibition of pathogen attachment by mimicking host cell surface charges or enzymatic degradation of polyanionic chains to prevent binding.