Viral surface glycoproteins mediating heparan sulfate proteoglycan-dependent entry

Viral surface glycoproteins mediating heparan sulfate proteoglycan (HSPG)-dependent entry are a functional class of viral proteins that facilitate the initial attachment of diverse viruses to host cells (NIH, 2021). These proteins, which include the spike protein of SARS-CoV-2, glycoprotein B (gB) of herpes simplex virus, and gp120 of HIV, typically possess clusters of basic amino acids that interact electrostatically with the negatively charged sulfate groups on cell-surface HSPGs (MDPI, 2021; ASM, 2005). This interaction serves as a primary docking step, concentrating virions at the cell surface and often triggering conformational changes or facilitating subsequent binding to more specific entry receptors (NIH, 2016). Because this mechanism is conserved across many human pathogens, these glycoproteins are attractive targets for broad-spectrum antiviral therapies, such as polyanionic entry inhibitors (Hilaris, 2016). Drugs like heparin, suramin, and carrageenan act by competitively masking the binding sites, thereby preventing viral adsorption and subsequent infection (Frontiers, 2024). However, therapeutic development faces challenges such as the ubiquitous nature of HSPGs in host physiology, which can lead to off-target effects, and the potential for viruses to adapt by increasing their affinity for other cell surface molecules (BioRxiv, 2025).

Other names

Viral attachment proteinsHSPG-binding viral proteinsViral entry glycoproteinsHeparan sulfate-binding viral proteins

Competitive inhibition of the electrostatic interaction between viral surface glycoproteins and host cell heparan sulfate proteoglycans (HSPGs), preventing viral attachment and entry.