The Sea Cucumber Thyonella gemmata Contains a Low Anticoagulant Sulfated Fucan with High Anti-SARS-CoV-2 Actions against Wild-Type and Delta Variants

Authors:

Rohini Dwivedi,  Marwa Farrag, Poonam Sharma, Deling Shi, Anter A. Shami, Sandeep K. Misra, Priya Ray, Jayanti Shukla, Fuming Zhang, Robert J. Linhardt, Joshua S. Sharp, Ritesh Tandon, and Vitor H. Pomin*

Affiliation:

Department of BioMolecular Sciences, University of Mississippi, Oxford, Mississippi 38677, United States

Center for Immunology and Microbial Research, Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, Mississippi 39216, United States

Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States

Department of Chemistry and Biochemistry, University of Mississippi, Oxford, Mississippi 38677, United States

Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Oxford, Mississippi 38677, United States

Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 39216, United States

Description:

In this work, we isolated two new sulfated glycans from the body wall of the sea cucumber Thyonella gemmata: one fucosylated chondroitin sulfate (TgFucCS) (17.5 ± 3.5% kDa) and one sulfated fucan (TgSF) (383.3 ± 2.1% kDa). NMR results showed the TgFucCS backbone composed of [→3)-β-N-acetylgalactosamine-(1→4)-β-glucuronic acid-(1→] with 70% 4-sulfated and 30% 4,6-disulfated GalNAc units and one-third of the GlcA units decorated at the C3 position with branching α-fucose (Fuc) units either 4-sulfated (65%) or 2,4-disulfated (35%) and the TgSF structure composed of a tetrasaccharide repeating unit of [→3)-α-Fuc2,4S-(1→2)-α-Fuc4S-(1→3)-α-Fuc2S-(1→3)-α-Fuc2S-(1→]n. Inhibitory properties of TgFucCS and TgSF were investigated using SARS-CoV-2 pseudovirus coated with S-proteins of the wild-type (Wuhan-Hu-1) or the delta (B.1.617.2) strains and in four different anticoagulant assays, comparatively with unfractionated heparin. Molecular binding to coagulation (co)-factors and S-proteins was investigated by competitive surface plasmon resonance spectroscopy. Among the two sulfated glycans tested, TgSF showed significant anti-SARS-CoV-2 activity against both strains together with low anticoagulant properties, indicating a good candidate for future studies in drug development.

Tags:

Carbohydrates
Chemical biology
SARS-CoV-2

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