Viral glycoprotein–host sulfated proteoglycan interface

The viral glycoprotein–host sulfated proteoglycan interface is a critical initial contact point for a wide range of human pathogens, including SARS-CoV-2, Herpes Simplex Virus (HSV), and Human Immunodeficiency Virus (HIV) (Cagno et al., 2019). This interface involves the interaction between positively charged domains on viral surface glycoproteins and the negatively charged sulfate groups of host cell surface heparan sulfate proteoglycans (HSPGs) (Liu & Thorp, 2002). HSPGs act as attachment factors that concentrate viral particles on the cell surface, thereby facilitating their subsequent interaction with specific entry receptors (Clausen et al., 2020). By serving as a primary docking site, this interface plays a pivotal role in the efficiency of viral infection and tissue tropism (Kamhi et al., 2013). Targeting this interaction offers a strategy for broad-spectrum antiviral therapy, as many unrelated viruses utilize similar electrostatic mechanisms for attachment. Drugs such as heparin mimetics and polyanionic compounds aim to competitively inhibit this binding, effectively masking the virus or the host cell surface to prevent entry (Cagno et al., 2019). However, therapeutic development must balance antiviral efficacy with the potential to disrupt the essential physiological roles of HSPGs in anticoagulation and growth factor signaling.

Other names

Viral attachment siteHSPG-viral glycoprotein complexHeparan sulfate-viral glycoprotein interfaceGlycosaminoglycan-viral protein interface

Competitive inhibition of viral attachment to host cell surface heparan sulfate proteoglycans