Anti-SARS-CoV-2 activity of rhamnan sulfate from Monostroma nitidum

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Authors
Song, Yuefan
He, Peng
Rodrigues, Andre L.
Datta, Payel
Tandon, Ritesh
Bates, John T.
Bierdeman, Michael A.
Chen, Chen
Dordick, Jonathan
Zhang, Fuming
Issue Date
2021-12-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
The COVID-19 pandemic is a major human health concern. The pathogen responsible for COVID-19, severe acute respiratory syndrome coronavirus 2 (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 to ACE2, heparan sulfate (HS) on the surface of host cells also plays a significant role as a co-receptor. Our previous studies demonstrated that sulfated glycans, such as heparin and fucoidans, show anti-COVID-19 activities. In the current study, rhamnan sulfate (RS), a polysaccharide with a rhamnose backbone from a green seaweed, Monostroma nitidum, was evaluated for binding to the S-protein from SARS-CoV-2 and inhibition of viral infectivity in vitro. The structural characteristics of RS were investigated by determining its monosaccharide composition and performing two-dimensional nuclear magnetic resonance. RS inhibition of the interaction of heparin, a highly sulfated HS, with the SARS-CoV-2 spike protein (from wild type and different mutant variants) was studied using surface plasmon resonance (SPR). In competitive binding studies, the IC50 of RS against the S-protein receptor binding domain (RBD) binding to immobilized heparin was 1.6 ng/mL, which is much lower than the IC50 for heparin (~750 ng/mL). RS showed stronger inhibition than heparin on the S-protein RBD or pseudoviral particles binding to immobilized heparin. Finally, in an in vitro cell-based assay, RS showed strong antiviral activities against wild type SARS-CoV-2 and the delta variant.
Description
Marine Drugs, 19, 685
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Full Citation
Anti-SARS-CoV-2 activity of rhamnan sulfate from Monostroma nitidum, Y. Song, P. He, A. L. Rodrigues, P. Datta, R. Tandon, J. T. Bates, M. Bierdeman, C. Chen, J. S. Dordick, F. Zhang, R. J. Linhardt, Marine Drugs, 19, 685, 2021.
Publisher
Multidisciplinary Digital Publishing Institute (MDPI)
Journal
Volume
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PubMed ID
DOI
ISSN
16603397
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