Seaweed-derived fucoidans and rhamnan sulfates serve as potent anti-SARS-CoV-2 agents with potential for prophylaxis

Song, Yuefan; Singh, Amit; Feroz, Maisha M.; Xu, Shirley; Zhang, Fuming; Jin, Weihua; Kumar, Ambrish; Azadi, Parastoo; Metzger, Dennis W.; Linhardt, Robert J.; Dordick, Jonathan S.

doi:10.1016/j.carbpol.2024.122156

Title: Seaweed-derived fucoidans and rhamnan sulfates serve as potent anti-SARS-CoV-2 agents with potential for prophylaxis

Journal Article · 15 April 2024 · Carbohydrate Polymers

DOI: https://doi.org/10.1016/j.carbpol.2024.122156 · OSTI ID:2530522

Song, Yuefan ^[1]; Singh, Amit ^[2]; Feroz, Maisha M. ^[1]; Xu, Shirley ^[1]; Zhang, Fuming ^[1]; Jin, Weihua ^[3]; Kumar, Ambrish ^[4]; Azadi, Parastoo ^[4]; Metzger, Dennis W. ^[5]; Linhardt, Robert J. ^[1]; Dordick, Jonathan S. ^[1]

Rensselaer Polytechnic Institute, Troy, NY (United States)
Albany Medical College, NY (United States)
Zheijiang University of Technology, Hangzhou (China)
University of Georgia, Athens, GA (United States)
Rensselaer Polytechnic Institute, Troy, NY (United States); Albany Medical College, NY (United States)

Seaweeds represent a rich source of sulfated polysaccharides with similarity to heparan sulfate, a facilitator of myriad virus host cell attachment. For this reason, attention has been drawn to their antiviral activity, including the potential for anti-SARS-CoV-2 activity. We have identified and structurally characterized several fucoidan extracts, including those from different species of brown macroalga, and a rhamnan sulfate from a green macroalga species. A high molecular weight fucoidan extracted from Saccharina japonica (FSjRPI-27), and a rhamnan sulfate extracted from Monostroma nitidum (RSMn), showed potent competitive inhibition of spike glycoprotein receptor binding to a heparin-coated SPR chip. This inhibition was also observed in cell-based assays using hACE2 HEK-293 T cells infected by pseudotyped SARS-CoV-2 virus with IC50 values <1 μg/mL. Effectiveness was demonstrated in vivo using hACE2–transgenic mice. Intranasal administration of FSjRPI-27 showed protection when dosed 6 h prior to and at infection, and then every 2 days post-infection, with 100 % survival and no toxicity at 104 plaque-forming units per mouse vs. buffer control. At 5-fold higher virus dose, FSjRPI-27 reduced mortality and yielded reduced viral titers in bronchioalveolar fluid and lung homogenates vs. buffer control. Furthermore, these findings suggest the potential application of seaweed-based sulfated polysaccharides as promising anti-SARS-CoV-2 prophylactics.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: University of Georgia, Athens, GA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division (CSGB)

Grant/Contract Number:: SC0015662

OSTI ID:: 2530522

Journal Information:: Carbohydrate Polymers, Journal Name: Carbohydrate Polymers Vol. 337; ISSN 0144-8617

Publisher:: Applied Science DirectCopyright Statement

Country of Publication:: United States

Language:: English

References (48)

Current status of oral pentosan polysulphate in bladder pain syndrome/interstitial cystitis Taneja, Rajesh International Urogynecology Journal, Vol. 32, Issue 5 https://doi.org/10.1007/s00192-020-04517-9	journal	September 2020
The positive effects of fucoidans extracted from the brown seaweed Saccharina japonica on protection against CCl4-induced liver injury Song, Yuefan; Wang, Qiukuan; He, Yunhai Journal of Applied Phycology, Vol. 29, Issue 4 https://doi.org/10.1007/s10811-017-1097-3	journal	April 2017
Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata—seasonal variation and impact of environmental factors Bruhn, Annette; Janicek, Tina; Manns, Dirk Journal of Applied Phycology, Vol. 29, Issue 6 https://doi.org/10.1007/s10811-017-1204-5	journal	July 2017
Extraction of laminarin from Saccharina latissima seaweed using cross-flow filtration Sterner, Martin; Gröndahl, Fredrik Journal of Applied Phycology, Vol. 33, Issue 3 https://doi.org/10.1007/s10811-021-02398-z	journal	February 2021
Structural studies on fucoidans from the brown seaweed Sargassum stenophyllum Duarte, Maria E. R.; Cardoso, Marc A.; Noseda, Miguel D. Carbohydrate Research, Vol. 333, Issue 4 https://doi.org/10.1016/S0008-6215(01)00149-5	journal	July 2001
Structure of the polysaccharide sheath from the B race of the green microalga Botryococcus braunii Heiss, Christian; Black, Ian; Ishihara, Mayumi Algal Research, Vol. 55 https://doi.org/10.1016/j.algal.2021.102252	journal	May 2021
Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions Kim, So Young; Jin, Weihua; Sood, Amika Antiviral Research, Vol. 181 https://doi.org/10.1016/j.antiviral.2020.104873	journal	September 2020
Structure of rhamnan sulfate from the green alga Monostroma nitidum and its anti-herpetic effect Lee, Jung-Bum; Koizumi, Seiji; Hayashi, Kyoko Carbohydrate Polymers, Vol. 81, Issue 3 https://doi.org/10.1016/j.carbpol.2010.03.014	journal	July 2010
A sulfated glucuronorhamnan from the green seaweed Monostroma nitidum: Characteristics of its structure and antiviral activity Wang, Shuyao; Wang, Wei; Hou, Lukuan Carbohydrate Polymers, Vol. 227 https://doi.org/10.1016/j.carbpol.2019.115280	journal	January 2020
A review on fucoidan antitumor strategies: From a biological active agent to a structural component of fucoidan-based systems Oliveira, Catarina; Neves, Nuno M.; Reis, Rui L. Carbohydrate Polymers, Vol. 239 https://doi.org/10.1016/j.carbpol.2020.116131	journal	July 2020
Fucoidan for cardiovascular application and the factors mediating its activities Yao, Yuan; Yim, Evelyn K. F. Carbohydrate Polymers, Vol. 270 https://doi.org/10.1016/j.carbpol.2021.118347	journal	October 2021
A state-of-the-art review on fucoidan as an antiviral agent to combat viral infections Pradhan, Biswajita; Nayak, Rabindra; Patra, Srimanta Carbohydrate Polymers, Vol. 291 https://doi.org/10.1016/j.carbpol.2022.119551	journal	September 2022
A highly regular fraction of a fucoidan from the brown seaweed Fucus distichus L. Bilan, Maria I.; Grachev, Alexey A.; Ustuzhanina, Nadezhda E. Carbohydrate Research, Vol. 339, Issue 3 https://doi.org/10.1016/j.carres.2003.10.028	journal	February 2004
Structure of a fucoidan from the brown seaweed Fucus serratus L. Bilan, Maria I.; Grachev, Alexey A.; Shashkov, Alexander S. Carbohydrate Research, Vol. 341, Issue 2 https://doi.org/10.1016/j.carres.2005.11.009	journal	February 2006
Structures and functions of algal glycans shape their capacity to sequester carbon in the ocean Bligh, Margot; Nguyen, Nguyen; Buck-Wiese, Hagen Current Opinion in Chemical Biology, Vol. 71 https://doi.org/10.1016/j.cbpa.2022.102204	journal	December 2022
SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2 Clausen, Thomas Mandel; Sandoval, Daniel R.; Spliid, Charlotte B. Cell, Vol. 183, Issue 4 https://doi.org/10.1016/j.cell.2020.09.033	journal	November 2020
Structural characterization and antitumor effects of fucoidans from brown algae Kjellmaniella crassifolia farmed in northern China Song, Yuefan; Wang, Qiukuan; Wang, Qingjun International Journal of Biological Macromolecules, Vol. 119 https://doi.org/10.1016/j.ijbiomac.2018.07.126	journal	November 2018
Inhibitory effects of fucoidan from Laminaria japonica against some pathogenic bacteria and SARS-CoV-2 depend on its large molecular weight Sun, Xiaona; Ai, Chunqing; Wen, Chengrong International Journal of Biological Macromolecules, Vol. 229 https://doi.org/10.1016/j.ijbiomac.2022.12.307	journal	February 2023
Preparation, structures, and biological functions of rhamnan sulfate from green seaweed of the genus Monostroma: A review Chi, Yongzhou; Jiang, Yanhui; Wang, Zhaoyu International Journal of Biological Macromolecules, Vol. 249 https://doi.org/10.1016/j.ijbiomac.2023.125964	journal	September 2023
Lack of active SARS-CoV-2 virus in a subset of PCR-positive COVID-19 congregate care patients Singh, Amit K.; Stellrecht, Kathleen A.; Arunachalam, Thilaka Journal of Clinical Virology, Vol. 141 https://doi.org/10.1016/j.jcv.2021.104879	journal	August 2021
Hypolipidemic effects of sulfated fucoidan from Kjellmaniella crassifolia through modulating the cholesterol and aliphatic metabolic pathways Peng, Yongbo; Wang, Yafang; Wang, Qiukuan Journal of Functional Foods, Vol. 51 https://doi.org/10.1016/j.jff.2018.10.013	journal	December 2018
Hydrogel-Forming Algae Polysaccharides: From Seaweed to Biomedical Applications Beaumont, Marco; Tran, Remy; Vera, Grace Biomacromolecules, Vol. 22, Issue 3 https://doi.org/10.1021/acs.biomac.0c01406	journal	February 2021
Structural Characterization of Fucoidan from Laminaria hyperborea : Assessment of Coagulation and Inflammatory Properties and Their Structure–Function Relationship Kopplin, Georg; Rokstad, Anne Mari; Mélida, Hugo ACS Applied Bio Materials, Vol. 1, Issue 6 https://doi.org/10.1021/acsabm.8b00436	journal	November 2018
Degradation of Eight Sulfated Polysaccharides Extracted from Red and Brown Algae and Its Impact on Structure and Pharmacological Activities Lahrsen, Eric; Schoenfeld, Ann-Kathrin; Alban, Susanne ACS Biomaterials Science & Engineering, Vol. 5, Issue 3 https://doi.org/10.1021/acsbiomaterials.8b01113	journal	February 2019
Heparan Sulfate Proteoglycans as Attachment Factor for SARS-CoV-2 Liu, Lin; Chopra, Pradeep; Li, Xiuru ACS Central Science, Vol. 7, Issue 6 https://doi.org/10.1021/acscentsci.1c00010	journal	June 2021
Structure and Biological Activity Analysis of Fucoidan Isolated from Sargassum siliquosum Wang, Shao-Hua; Huang, Chih-Yu; Chen, Chun-Yen ACS Omega, Vol. 5, Issue 50 https://doi.org/10.1021/acsomega.0c04591	journal	December 2020
Well-Defined Heparin Mimetics Can Inhibit Binding of the Trimeric Spike of SARS-CoV-2 in a Length-Dependent Manner Sun, Lifeng; Chopra, Pradeep; Tomris, Ilhan JACS Au, Vol. 3, Issue 4 https://doi.org/10.1021/jacsau.3c00042	journal	April 2023
Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro Kwon, Paul S.; Oh, Hanseul; Kwon, Seok-Joon Cell Discovery, Vol. 6, Issue 1 https://doi.org/10.1038/s41421-020-00192-8	journal	July 2020
Heparan sulfate assists SARS-CoV-2 in cell entry and can be targeted by approved drugs in vitro Zhang, Qi; Chen, Catherine Zhengzheng; Swaroop, Manju Cell Discovery, Vol. 6, Issue 1 https://doi.org/10.1038/s41421-020-00222-5	journal	November 2020
Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions Kwon, Paul S.; Xu, Shirley; Oh, Hanseul Communications Biology, Vol. 6, Issue 1 https://doi.org/10.1038/s42003-023-04789-z	journal	April 2023
Revisiting monosaccharide analysis – quantitation of a comprehensive set of monosaccharides using dynamic multiple reaction monitoring Xu, Gege; Amicucci, Matthew J.; Cheng, Zhi The Analyst, Vol. 143, Issue 1 https://doi.org/10.1039/C7AN01530E	journal	January 2018
Revised structure model of norovirus-binding fucoidan from Undaria pinnatifida: oligofucose chains branch off from a β6-galactane Hanisch, Franz-Georg Glycobiology, Vol. 33, Issue 7 https://doi.org/10.1093/glycob/cwad039	journal	May 2023
NMR characterization and molecular modeling of fucoidan showing the importance of oligosaccharide branching in its anticomplementary activity Clément, Marie-Jeanne; Tissot, Bérangère; Chevolot, Lionel Glycobiology, Vol. 20, Issue 7 https://doi.org/10.1093/glycob/cwq046	journal	March 2010
Low-level resource partitioning supports coexistence among functionally redundant bacteria during successional dynamics Yu, Xiaoqian Annie; McLean, Craig; Hehemann, Jan-Hendrik The ISME Journal, Vol. 18, Issue 1 https://doi.org/10.1093/ismejo/wrad013	journal	January 2024
Glycosaminoglycans in infectious disease: Glycosaminoglycans in infectious disease Kamhi, Eyal; Joo, Eun Ji; Dordick, Jonathan S. Biological Reviews, Vol. 88, Issue 4 https://doi.org/10.1111/brv.12034	journal	March 2013
Study on Branched Structure–Physiological Activity Relationship of Fucoidan Yuguchi, Yoshiaki; Ly, Bui Minh; Van Nguyen, Bui Chemistry Letters, Vol. 45, Issue 7 https://doi.org/10.1246/cl.160189	journal	July 2016
Infection and transmission of SARS‐CoV‐2 depend on heparan sulfate proteoglycans Bermejo‐Jambrina, Marta; Eder, Julia; Kaptein, Tanja M. The EMBO Journal, Vol. 40, Issue 20 https://doi.org/10.15252/embj.2020106765	journal	September 2021
Antitumor activity of fucoidan: a systematic review and meta-analysis Cao, Ling-Min; Sun, Zao-Xi; Makale, Emmanuel Costantine Translational Cancer Research, Vol. 10, Issue 12 https://doi.org/10.21037/tcr-21-1733	journal	December 2021
Heparan Sulfate Facilitates Spike Protein-Mediated SARS-CoV-2 Host Cell Invasion and Contributes to Increased Infection of SARS-CoV-2 G614 Mutant and in Lung Cancer Yue, Jingwen; Jin, Weihua; Yang, Hua Frontiers in Molecular Biosciences, Vol. 8 https://doi.org/10.3389/fmolb.2021.649575	journal	June 2021
Interactions between heparin and SARS-CoV-2 spike glycoprotein RBD from omicron and other variants Gelbach, Adrianne L.; Zhang, Fuming; Kwon, Seok-Joon Frontiers in Molecular Biosciences, Vol. 9 https://doi.org/10.3389/fmolb.2022.912887	journal	August 2022
Therapeutic Effects of Fucoidan: A Review on Recent Studies Luthuli, Sibusiso; Wu, Siya; Cheng, Yang Marine Drugs, Vol. 17, Issue 9 https://doi.org/10.3390/md17090487	journal	August 2019
Marine Sulfated Polysaccharides as Promising Antiviral Agents: A Comprehensive Report and Modeling Study Focusing on SARS CoV-2 Salih, Abdalla E. M.; Thissera, Bathini; Yaseen, Mohammed Marine Drugs, Vol. 19, Issue 8 https://doi.org/10.3390/md19080406	journal	July 2021
Antiviral Activity of Carrageenans and Processing Implications Álvarez-Viñas, Milena; Souto, Sandra; Flórez-Fernández, Noelia Marine Drugs, Vol. 19, Issue 8 https://doi.org/10.3390/md19080437	journal	July 2021
Anti-SARS-CoV-2 Activity of Rhamnan Sulfate from Monostroma nitidum Song, Yuefan; He, Peng; Rodrigues, Andre L. Marine Drugs, Vol. 19, Issue 12 https://doi.org/10.3390/md19120685	journal	November 2021
Important Determinants for Fucoidan Bioactivity: A Critical Review of Structure-Function Relations and Extraction Methods for Fucose-Containing Sulfated Polysaccharides from Brown Seaweeds Ale, Marcel Tutor; Mikkelsen, Jørn D.; Meyer, Anne S. Marine Drugs, Vol. 9, Issue 10 https://doi.org/10.3390/md9102106	journal	October 2011
Immunomodulatory and Anti-Inflammatory Effects of Fucoidan: A Review Apostolova, Elisaveta; Lukova, Paolina; Baldzhieva, Alexandra Polymers, Vol. 12, Issue 10 https://doi.org/10.3390/polym12102338	journal	October 2020
Antiviral Strategies Using Natural Source-Derived Sulfated Polysaccharides in the Light of the COVID-19 Pandemic and Major Human Pathogenic Viruses Ray, Bimalendu; Ali, Imran; Jana, Subrata Viruses, Vol. 14, Issue 1 https://doi.org/10.3390/v14010035	journal	December 2021
Structural Characteristics of Heparin Binding to SARS-CoV-2 Spike Protein RBD of Omicron Sub-Lineages BA.2.12.1, BA.4 and BA.5 Shi, Deling; Bu, Changkai; He, Peng Viruses, Vol. 14, Issue 12 https://doi.org/10.3390/v14122696	journal	December 2022

Similar Records

Bifunctional effects of fucoidan on the expression of inducible nitric oxide synthase

Journal Article · 2006 · Biochemical and Biophysical Research Communications · OSTI ID:20854374

Yang, Jin Won; Yoon, Se Young; Oh, Soo Jin; +2 more

Postinfection treatment with a protease inhibitor increases survival of mice with a fatal SARS-CoV-2 infection

Journal Article · 2021 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1816161

Dampalla, Chamandi S.; Zheng, Jian; Perera, Krishani Dinali; +10 more

Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2

Journal Article · 2022 · Nature Communications · OSTI ID:1846287

El-Shennawy, Lamiaa; Hoffmann, Andrew D.; Dashzeveg, Nurmaa Khund; +33 more

Related Subjects

60 APPLIED LIFE SCIENCES
Fractionation
Fucoidan
In vitro anti-SARS-CoV-2 activity
In vivo prophylaxis
Rhamnan sulfate
SARS-CoV-2

Title: Seaweed-derived fucoidans and rhamnan sulfates serve as potent anti-SARS-CoV-2 agents with potential for prophylaxis

Citation Formats

References (48)

Similar Records

Related Subjects