The diverse role of heparan sulfate and other GAGs in SARS-CoV-2 infections and therapeutics

Eilts, Friederike; Bauer, Sarah; Fraser, Keith; Dordick, Jonathan S.; Wolff, Michael W.; Linhardt, Robert J.; Zhang, Fuming

doi:10.1016/j.carbpol.2022.120167

Cited by 14 publications

(12 citation statements)

References 118 publications

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“…SARS-CoV-2 virions enrich their local concentration through these non-specific interactions before binding to the ACE2 receptor. Docking studies suggest that heparin or HS bind to a site adjacent to the ACE2 binding site, and this is substantiated by experimental results showing ACE2 and HS can independently bind the S-protein 15 , 17 . In the present work, we examined the ability of suramin to bind to RBDs of several SARS-CoV-2 variants and elucidated the mechanism by which this potential repositioned drug may serve to inhibit viral entry and propagation.…”

Section: Introductionmentioning

confidence: 83%

Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions

Kwon

et al. 2023

Commun Biol

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SARS-CoV-2 receptor binding domains (RBDs) interact with both the ACE2 receptor and heparan sulfate on the surface of host cells to enhance SARS-CoV-2 infection. We show that suramin, a polysulfated synthetic drug, binds to the ACE2 receptor and heparan sulfate binding sites on the RBDs of wild-type, Delta, and Omicron variants. Specifically, heparan sulfate and suramin had enhanced preferential binding for Omicron RBD, and suramin is most potent against the live SARS-CoV-2 Omicron variant (B.1.1.529) when compared to wild type and Delta (B.1.617.2) variants in vitro. These results suggest that inhibition of live virus infection occurs through dual SARS-CoV-2 targets of S-protein binding and previously reported RNA-dependent RNA polymerase inhibition and offers the possibility for this and other polysulfated molecules to be used as potential therapeutic and prophylactic options against COVID-19.

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Section: Introductionmentioning

confidence: 83%

Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions

Kwon

et al. 2023

Commun Biol

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“…These molecules have the potential to bind to gp120 and the S protein and block the viruses from being able to recognize/bind to vulnerable host cells bearing the primary viral receptors, such as CD4 + helper T cells, as well as ACE-2-bearing epithelial tissues, in HIV-and SARS-CoV-2mediated infection events, respectively. 6 Earlier studies conducted in our laboratory provided proof of concept for this approach. Other groups have also explored glycodendrimers for these applications.…”

Section: ■ Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

“…It is this type of interaction that our research seeks to block through the design and synthesis of HSPG-analogues in the form of sulfated glycodendrimers. These molecules have the potential to bind to gp120 and the S protein and block the viruses from being able to recognize/bind to vulnerable host cells bearing the primary viral receptors, such as CD4 + helper T cells, as well as ACE-2-bearing epithelial tissues, in HIV- and SARS-CoV-2-mediated infection events, respectively …”

Section: Introductionmentioning

confidence: 99%

“…Viruses such as HIV and SARS-CoV-2 as well as many other pathogens utilize the ubiquitous cell surface heparan sulfate proteoglycans (HSPGs) in the early-stage binding of the surface glycoproteins such as gp120 and the S protein of HIV and SARS-CoV-2, respectively. 6 HSPGs are important in normal cell functioning in many ways, including embryonic development, adult homeostasis, and aging. 7 They are also implicated in many disease states, which includes serving as a coreceptor for virus concentration at the cell surface and presentation to the primary receptors, as is seen with HIV, SARS-CoV-2, and many other diverse types of viruses.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Nuclear Magnetic Resonance Structural Evaluation of Oxime-Linked Oligosialic Acid-Based Glycodendrimers

et al. 2023

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A series of four oxime-linked octavalent sialic acid and oligosialic acid poly(ether amidoamine) glycodendrimers were synthesized. In the attachment of the sialic acids to the dendrimer core, chemoselective oxime bonds were formed between the unprotected sugars (sialic acid or α-2,8-linked di- through tetra-sialic acids) and the aminooxy-terminated dendrimer core in a microwave-mediated reaction, resulting in good to excellent yields (58–100%) of the fully functionalized octavalent glycodendrimers. Next, using a combination of 1D and 2D nuclear magnetic resonance and working from the inside outward, we employed a systematic method to assign the proton and carbon signals starting with the smallest linkers and dendrimer cores and moving gradually up to the completed octavalent glycodendrimers. Through this approach, the assignment of the protons and carbons was possible, including the E- and Z-isomers related to the oxime dendrimer to sugar connections and relative quantities of each. These glycodendrimers were designed as broad-spectrum inhibitors of viral pathogens.

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PRO-2000 exhibits SARS-CoV-2 antiviral activity by interfering with spike-heparin binding

et al. 2023

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The diverse role of heparan sulfate and other GAGs in SARS-CoV-2 infections and therapeutics

Cited by 14 publications

References 118 publications

Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions

Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions

Synthesis and Nuclear Magnetic Resonance Structural Evaluation of Oxime-Linked Oligosialic Acid-Based Glycodendrimers

PRO-2000 exhibits SARS-CoV-2 antiviral activity by interfering with spike-heparin binding

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