Is heparan sulfate a target for inhibition of RNA virus infection?

Abstract

Heparan sulfate (HS) is a linear polysaccharide attached to a core protein, forming heparan sulfate proteoglycans (HSPGs) that are ubiquitously expressed on the surface of almost all mammalian cells and the extracellular matrix. HS orchestrates the binding of various signal molecules to their receptors, thus, regulating many biological processes, including homeostasis, metabolism, and various pathological processes. Due to its wide distribution and negatively charged properties, HS is exploited by many viruses as a co-factor to attach to host cells. Therefore, inhibition of the interaction between virus and HS is proposed as a promising approach to mitigate viral infection, including SARS-CoV-2. In this review, we summarize the interaction manners of HS with viruses with focus on significant pathogenic RNA viruses, including alphaviruses, flaviviruses, and coronaviruses. We also provide an overview of the challenges we may face when using HS-mimetics as antivirals for clinical treatment. More studies are needed to provide a further understanding of the interplay between HS and viruses both in vitro and in vivo, which will favor the development of specific antiviral inhibitors.

Well-Defined Heparin Mimetics Can Inhibit Binding of the Trimeric Spike of SARS-CoV-2 in a Length-Dependent Manner

“…Multiple viruses employ HS as a receptor or coreceptor for cell attachment. − It is the expectation that glycan microarray screening to identify monovalent binding partners combined with the strategy described here to prepare multivalent heparin mimetics will provide potent inhibitors. Furthermore, next-generation heparins have the potential to act as therapeutics for multiple diseases including inflammatory and neurological diseases, cancer, and wound healing. , It is the expectation that the mimetics described here will facilitate harnessing the biomedical potential of heparin.…”

Reappraising host cellular factors involved in attachment and entry to develop antiviral strategies against porcine reproductive and respiratory syndrome virus

“…HS is a linear, unbranched, negatively charged polysaccharide attached to various cell surface or extracellular matrix proteins. It mediates cellular signaling, maintains homeostasis, and regulates cellular growth and metabolism ( Ling et al, 2022 ). At first, HS was found bound by PRRSV matrix protein during viral attachment to PAMs ( Delputte et al, 2002 , 2005 ).…”

Resveratrol inhibits respiratory syncytial virus replication by targeting heparan sulfate proteoglycans

“…18 Numerous viruses, such as coronaviruses, flaviviruses, retroviruses, and herpesviruses, utilize heparan sulfate proteoglycans (HSPGs) as receptors for their attachment ligands. 19 HSPGs are present on the surface of nearly all eukaryotic cells, serving as attachment factors for many viruses. 19,20 Targeting the interaction between RSV and HSPGs provides a promising avenue for developing novel RSV infection inhibitors.…”

“…19 HSPGs are present on the surface of nearly all eukaryotic cells, serving as attachment factors for many viruses. 19,20 Targeting the interaction between RSV and HSPGs provides a promising avenue for developing novel RSV infection inhibitors. 21 The binding of viruses to HSPGs typically happens when clusters of positively charged amino acids on viral attachment ligand proteins interact with the negatively charged sulfated groups of heparan sulfate in the cell surface glycocalyx.…”

“…18,[22][23][24] Disturbing the interaction between HSPGs and viruses is believed to be a promising approach to reduce viral infection. 19 Indeed, researchers have developed methods targeting HSPGs with the purpose of obstructing RSV's attachment to HSPGs, consequently exerting antiviral effects. Numerous HSPG-mimicking materials, including heparin, sulfated polysaccharides, as well as sulfonic-acid-decorated polymers, dendrimers, and nanoparticles, have been tested and demonstrated robust anti-RSV effects in in vitro and in vivo studies.…”