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dc.rights.licenseCC BY — Creative Commons Attribution
dc.contributor.authorKim, Seon Beom
dc.contributor.authorZoepfl, Mary
dc.contributor.authorSamanta, Priyanka
dc.contributor.authorZhang, Fuming
dc.contributor.authorXia, Ke
dc.contributor.authorThara, Reena
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorDoerksen, Robert J.
dc.contributor.authorMcVoy, Michael A.
dc.contributor.authorPomin, Vitor H.
dc.identifier.citationFractionation of sulfated galactan from the red alga Botryocladia occidentalis separates its anticoagulant and anti-SARS-CoV-2 properties, S. B. Kim, M. Zoepfl, P. Samanta, F. Zhang, K. Xia, R. Thara, R. J. Linhardt, R. J. Doerksen, M. McVoy, V. H. Pomin, Journal of Biological Chemistry, 298, 101856, 2022.
dc.descriptionJournal of Biological Chemistry, 298, 101856
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractSulfation pattern and molecular weight (MW) play a key role in the biological actions of sulfated glycans. Besides anticoagulant effects, certain sulfated glycans can also exhibit anti-SARS-CoV-2 properties. To develop a more selective antiviral carbohydrate, an efficient strategy to separate these two actions is required. In this work, low MW fractions derived from the red alga Botryocladia occidentalis sulfated galactan (BoSG) were generated, structurally characterized, and tested for activity against SARS-CoV-2 and blood coagulation. The lowest MW fraction was found to be primarily composed of octasaccharides of monosulfated monosaccharides. Unlike heparin or native BoSG, we found that hydrolyzed BoSG products had weak anticoagulant activities as seen by aPTT and inhibitory assays using purified cofactors. In contrast, lower MW BoSG-derivatives retained anti-SARS-CoV-2 activity using SARS-CoV-2 spike (S)-protein pseudotyped lentivirus vector in HEK-293T-hACE2 cells monitored by GFP. Surface plasmon resonance confirmed that longer chains are necessary for BoSG to interact with coagulation cofactors but is not required for interactions with certain S-protein variants. We observed distinct affinities of BoSG derivatives for the S-proteins of different SARS-CoV-2 strains, including WT, N501Y (Alpha), K417T/E484K/N501Y (Gamma), and L542R (Delta) mutants, and stronger affinity for the N501Y-containing variants. Docking of the four possible monosulfated BoSG disaccharides in interactions with the N501Y mutant S-protein predicted potential binding poses of the BoSG constructs and favorable binding in close proximity to the 501Y residue. Our results demonstrate that depolymerization and fractionation of BoSG are an effective strategy to segregate its anticoagulant property from its anti-SARS-CoV-2 action.
dc.description.sponsorshipNational Natural Science Foundation of China
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofJournal of Biological Chemistry
dc.rightsAttribution 3.0 United States*
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleFractionation of sulfated galactan from the red alga Botryocladia occidentalis separates its anticoagulant and anti-SARS-CoV-2 propertiesen_US
dcterms.accessRightsOpen Access
dcterms.accessRightsA full text version is available in DSpace@RPI
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dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)

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Except where otherwise noted, this item's license is described as CC BY — Creative Commons Attribution