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Glycobiology
2023 Jan 08;331:75-85. doi: 10.1093/glycob/cwac063.
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Anti-SARS-CoV-2 and anticoagulant properties of Pentacta pygmaea fucosylated chondroitin sulfate depend on high molecular weight structures.
Dwivedi R
,
Sharma P
,
Eilts F
,
Zhang F
,
Linhardt RJ
,
Tandon R
,
Pomin VH
.
Abstract
Fucosylated chondroitin sulfate (FucCS) is a unique marine glycosaminoglycan that exhibits diverse biological functions, including antiviral and anticoagulant activity. In previous work, the FucCS derived from Pentacta pygmaea (PpFucCS) showed moderate anticoagulant effect but high inhibitory activity against the Wuhan strain of severe acute respiratory syndrome coronavirus (SARS-CoV-2). In this study, we perform free-radical depolymerization of PpFucCS by the copper-based Fenton method to generate low molecular weight (MW) oligosaccharides. PpFucCS oligosaccharides were structurally analyzed by 1H nuclear magnetic resonance spectroscopy and were used to conduct structure-activity relationship studies regarding their effects against SARS-CoV-2 and clotting. Anticoagulant properties were measured by activated partial thromboplastin time, protease (factors Xa and IIa) inhibition by serine protease inhibitors (antithrombin [AT] and heparin cofactor II [HCII]), and competitive surface plasmon resonance (SPR) assay using AT, HCII, and IIa. Anti-SARS-CoV-2 properties were measured by the concentration-response inhibitory curves of HEK-293T-human angiotensin-converting enzyme-2 cells infected with a baculovirus pseudotyped SARS-CoV-2 Delta variant spike (S)-protein and competitive SPR assays using multiple S-proteins (Wuhan, N501Y [Alpha], K417T/E484K/N501Y [Gamma], L542R [Delta], and Omicron [BA.2 subvariant]). Cytotoxicity of native PpFucCS and oligosaccharides was also assessed. The PpFucCS-derived oligosaccharide fraction of the highest MW showed great anti-SARS-CoV-2 Delta activity and reduced anticoagulant properties. Results have indicated no cytotoxicity and MW dependency on both anti-SARS-CoV-2 and anticoagulant effects of PpFucCS, as both actions were reduced accordingly to the MW decrease of PpFucCS. Our results demonstrate that the high-MW structures of PpFucCS is a key structural element to achieve the maximal anti-SARS-CoV-2 and anticoagulant effects.
Aleem,
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Aleem,
Emerging Variants of SARS-CoV-2 and Novel Therapeutics Against Coronavirus (COVID-19)
2024,
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Belouzard,
Mechanisms of coronavirus cell entry mediated by the viral spike protein.
2012,
Pubmed
Clausen,
SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2.
2020,
Pubmed
Cosar,
SARS-CoV-2 Mutations and their Viral Variants.
2022,
Pubmed
Dwivedi,
Structural and kinetic analyses of holothurian sulfated glycans suggest potential treatment for SARS-CoV-2 infection.
2021,
Pubmed
,
Echinobase
Farias,
Structure and anticoagulant activity of sulfated galactans. Isolation of a unique sulfated galactan from the red algae Botryocladia occidentalis and comparison of its anticoagulant action with that of sulfated galactans from invertebrates.
2000,
Pubmed
Guimond,
Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction.
2022,
Pubmed
Harvey,
SARS-CoV-2 variants, spike mutations and immune escape.
2021,
Pubmed
Hu,
Characteristics of SARS-CoV-2 and COVID-19.
2021,
Pubmed
Kim,
Fractionation of sulfated galactan from the red alga Botryocladia occidentalis separates its anticoagulant and anti-SARS-CoV-2 properties.
2022,
Pubmed
Li,
Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments.
2016,
Pubmed
,
Echinobase
Li,
Fucosylated chondroitin sulfate oligosaccharides exert anticoagulant activity by targeting at intrinsic tenase complex with low FXII activation: Importance of sulfation pattern and molecular size.
2017,
Pubmed
,
Echinobase
Mourão,
Perspective on the use of sulfated polysaccharides from marine organisms as a source of new antithrombotic drugs.
2015,
Pubmed
Oliveira,
Structural and functional analyses of biosimilar enoxaparins available in Brazil.
2015,
Pubmed
Pereira,
Structure and anticoagulant activity of sulfated fucans. Comparison between the regular, repetitive, and linear fucans from echinoderms with the more heterogeneous and branched polymers from brown algae.
1999,
Pubmed
,
Echinobase
Planas,
Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization.
2021,
Pubmed
Saito,
Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation.
2022,
Pubmed
Shyr,
Drug Discovery Strategies for SARS-CoV-2.
2020,
Pubmed
Tandon,
Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives.
2021,
Pubmed
Thakur,
SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines.
2022,
Pubmed
Tian,
The Global Epidemic of the SARS-CoV-2 Delta Variant, Key Spike Mutations and Immune Escape.
2021,
Pubmed
Vasconcelos,
Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives.
2018,
Pubmed
,
Echinobase
Wu,
Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase.
2015,
Pubmed
Xiu,
Inhibitors of SARS-CoV-2 Entry: Current and Future Opportunities.
2020,
Pubmed
Yan,
Heparan sulfates from bat and human lung and their binding to the spike protein of SARS-CoV-2 virus.
2021,
Pubmed
