Heparan sulfate proteoglycan co-receptor (HSPG)

Heparan sulfate proteoglycans (HSPGs) are ubiquitous glycoproteins found on the cell surface and within the extracellular matrix, consisting of a core protein covalently linked to heparan sulfate glycosaminoglycan chains. In the context of viral infections, particularly SARS-CoV-2, HSPGs serve as essential co-receptors that facilitate the initial attachment of the virus to the host cell membrane (Clausen et al., 2020, Cell). The viral spike protein interacts with the negatively charged sulfate groups on the HSPG chains, which promotes a conformational change or increases the local concentration of the virus, allowing it to efficiently engage its primary receptor, Angiotensin-converting enzyme 2 (ACE2). This interaction forms a ternary complex (Spike-HSPG-ACE2) that is critical for viral entry and subsequent infection. Because of this role, HSPGs and their associated interfaces are significant therapeutic targets; heparin and other glycan mimetics are being explored to competitively inhibit viral binding and reduce infectivity. Beyond viral entry, HSPGs are involved in regulating various physiological processes, including inflammation and tumor metastasis, making them versatile but complex targets for drug development.

Other names

Heparan sulfate proteoglycanHSPGSyndecanGlypicanCell surface glycanViral attachment factorHeparan sulfate co-receptor

Competitive inhibition of viral spike protein binding to host cell surface heparan sulfate proteoglycans, thereby preventing the formation of the ternary complex required for ACE2-mediated viral entry.