Structural and kinetic analyses of holothurian sulfated glycans suggest potential treatment for SARS-CoV-2 infection

Dwivedi, Rohini; Samanta, Priyanka; Sharma, Poonam; Zhang, Fuming; Mishra, Sushil Kumar; Kucheryavy, Pavel; Kim, Seon Beom; Aderibigbe, AyoOluwa O.; Linhardt, Robert J.; Tandon, Ritesh; Doerksen, Robert J.; Pomin, Vitor H.

doi:10.1016/j.jbc.2021.101207

Cited by 37 publications

(99 citation statements)

References 104 publications

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“…The ideal anti-SARS-CoV-2 marine sulfated glycan would be devoid of anticoagulant effects ( 67 ). The native BoSG, a hydrolyzed unfractionated BoSG sample (SGhd) and the four fractions of different MWs derived from BoSG (Fr1-Fr4) were subjected to in vitro anticoagulant assays to investigate the impact of MW on the anticoagulant action of BoSG.…”

Section: Resultsmentioning

confidence: 99%

“…A heparin disaccharide was also constructed and docked for comparison. The binding site examined in this study was the same one previously used for the holothurian sulfated glycans in binding analyses to the wild type and the N501Y mutant S-protein RBDs ( 67 ). The docking data are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The 3D structure of the S-protein RBD was obtained from the Protein Data Bank (PDB: 6M0J) ( 14 ). The published equilibrated 3D structure of the mutant variant N501Y S-protein RBD ( 67 ) was used for molecular docking.…”

Section: Methodsmentioning

confidence: 99%

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Fractionation of sulfated galactan from the red alga Botryocladia occidentalis separates its anticoagulant and anti-SARS-CoV-2 properties

Kim

Zoepfl

Samanta

et al. 2022

Journal of Biological Chemistry

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Fractionation of sulfated galactan from the red alga Botryocladia occidentalis separates its anticoagulant and anti-SARS-CoV-2 properties

Kim

Zoepfl

Samanta

et al. 2022

Journal of Biological Chemistry

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“…We and others have shown that sulfated polysaccharides inhibit the interaction between HS and the S-protein, including heparin, fucoidans, and rhamnan sulfate [24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 92%

“…Finally, an in vitro SARS-CoV-2 pseudotyped viral particle neutralization assay was performed. Sulfated glycans such as heparin have been shown to inhibit viral infection by interacting with the SARS-CoV-2 spike protein [24][25][26][27]. Thus, we investigated the ability of PPS and MPS to inhibit viral particle entry using a cell-based neutralization assay.…”

Section: In Vitro Sars-cov-2 Pseudotyped Viral Particle Neutralizationmentioning

confidence: 99%

Potential Anti-SARS-CoV-2 Activity of Pentosan Polysulfate and Mucopolysaccharide Polysulfate

Zhang

Rodrigues

et al. 2022

Pharmaceuticals

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With the increased prevalence of new SARS-CoV-2 variants of concern, such as Delta and Omicron, the COVID-19 pandemic has become an ongoing human health disaster, killing millions worldwide. SARS-CoV-2 invades its host through the interaction of its spike (S) protein with a host cell receptor, angiotensin-converting enzyme 2 (ACE2). In addition, heparan sulfate (HS) on the surface of host cells plays an important role as a co-receptor for this viral pathogen–host cell interaction. Our previous studies demonstrated that many sulfated glycans, such as heparin, fucoidans, and rhamnan sulfate have anti-SARS-CoV-2 activities. In the current study, a small library of sulfated glycans and highly negatively charged compounds, including pentosan polysulfate (PPS), mucopolysaccharide polysulfate (MPS), sulfated lactobionic acid, sulodexide, and defibrotide, was assembled and evaluated for binding to the S-proteins and inhibition of viral infectivity in vitro. These compounds inhibited the interaction of the S-protein receptor-binding domain (RBD) (wild type and different variants) with immobilized heparin, a highly sulfated HS, as determined using surface plasmon resonance (SPR). PPS and MPS showed the strongest inhibition of interaction of heparin and S-protein RBD. The competitive binding studies showed that the IC50 of PPS and MPS against the S-protein RBD binding to immobilized heparin was ~35 nM and ~9 nM, respectively, much lower than the IC50 for soluble heparin (IC50 = 56 nM). Both PPS and MPS showed stronger inhibition than heparin on the S-protein RBD or spike pseudotyped lentiviral particles binding to immobilized heparin. Finally, in an in vitro cell-based assay, PPS and MPS exhibited strong antiviral activities against pseudotyped viral particles of SARS-CoV-2 containing wild-type or Delta S-proteins.

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Nuclear magnetic resonance‐based structural elucidation of novel marine glycans and derived oligosaccharides

Dwivedi

Maurya

Ahmed

et al. 2023

Magnetic Reson in Chemistry

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Marine glycans of defined structures are unique representatives among all kinds of structurally complex glycans endowed with important biological actions. Besides their unique biological properties, these marine sugars also enable advanced structure–activity relationship (SAR) studies given their distinct and defined structures. However, the natural high molecular weights (MWs) of these marine polysaccharides, sometimes even bigger than 100 kDa, pose a problem in many biophysical and analytical studies. Hence, the preparation of low MW oligosaccharides becomes a strategy to overcome the problem. Regardless of the polymeric or oligomeric lengths of these molecules, structural elucidation is mandatory for SAR studies. For this, nuclear magnetic resonance (NMR) spectroscopy plays a pivotal role. Here, we revisit the NMR‐based structural elucidation of a series of marine sulfated poly/oligosaccharides discovered in our laboratory within the last 2 years. This set of structures includes the α‐glucan extracted from the bivalve Marcia hiantina; the two sulfated galactans extracted from the red alga Botryocladia occidentalis; the fucosylated chondroitin sulfate isolated from the sea cucumber Pentacta pygmaea; the oligosaccharides produced from the fucosylated chondroitin sulfates from this sea cucumber species and from another species, Holothuria floridana; and the sulfated fucan from this later species. Specific 1H and 13C chemical shifts, generated by various 1D and 2D homonuclear and heteronuclear NMR spectra, are exploited as the primary source of information in the structural elucidation of these marine glycans.

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Structural and kinetic analyses of holothurian sulfated glycans suggest potential treatment for SARS-CoV-2 infection

Cited by 37 publications

References 104 publications

Fractionation of sulfated galactan from the red alga Botryocladia occidentalis separates its anticoagulant and anti-SARS-CoV-2 properties

Fractionation of sulfated galactan from the red alga Botryocladia occidentalis separates its anticoagulant and anti-SARS-CoV-2 properties

Potential Anti-SARS-CoV-2 Activity of Pentosan Polysulfate and Mucopolysaccharide Polysulfate

Nuclear magnetic resonance‐based structural elucidation of novel marine glycans and derived oligosaccharides

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