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The structure-activity relationship of the interactions of SARS-CoV-2 spike glycoproteins with glucuronomannan and sulfated galactofucan from Saccharina japonica.
Jin, Weihua; Zhang, Wenjing; Mitra, Dipanwita; McCandless, Martin G; Sharma, Poonam; Tandon, Ritesh; Zhang, Fuming; Linhardt, Robert J.
  • Jin W; College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. Electronic address: jinweihua@zjut
  • Zhang W; Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
  • Mitra D; Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • McCandless MG; Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Sharma P; Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Tandon R; Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Zhang F; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. Electronic address: zhangf2@rpi.edu.
  • Linhardt RJ; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Departments of Biological Science, Chemistry and Chemical Biology and Biomedical Engineering, Center for Biotechnology and Interdisciplina
Int J Biol Macromol ; 163: 1649-1658, 2020 Nov 15.
Article in English | MEDLINE | ID: covidwho-792418
ABSTRACT
The SARS-CoV-2 spike glycoproteins (SGPs) and human angiotensin converting enzyme 2 (ACE2) are the two key targets for the prevention and treatment of COVID-19. Host cell surface heparan sulfate (HS) is believed to interact with SARS-CoV-2 SGPs to facilitate host cell entry. In the current study, a series of polysaccharides from Saccharina japonica were prepared to investigate the structure-activity relationship on the binding abilities of polysaccharides (oligosaccharides) to pseudotype particles, including SARS-CoV-2 SGPs, and ACE2 using surface plasmon resonance. Sulfated galactofucan (SJ-D-S-H) and glucuronomannan (Gn) displayed strongly inhibited interaction between SARS-CoV-2 SGPs and heparin while showing negligible inhibition of the interaction between SARS-CoV-2 SGPs and ACE2. The IC50 values of SJ-D-S-H and Gn in blocking heparin SGP binding were 27 and 231 nM, respectively. NMR analysis showed that the structure of SJ-D-S-H featured with a backbone of 1, 3-linked α-L-Fucp residues sulfated at C4 and C2/C4 and 1, 3-linked α-L-Fucp residues sulfated at C4 and branched with 1, 6-linked ß-D-galacto-biose; Gn had a backbone of alternating 1, 4-linked ß-D-GlcAp residues and 1, 2-linked α-D-Manp residues. The sulfated galactofucan and glucuronomannan showed strong binding ability to SARS-CoV-2 SGPs, suggesting that these polysaccharides might be good candidates for preventing and/or treating SARS-CoV-2.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Polysaccharides / Coronavirus Infections / Spike Glycoprotein, Coronavirus / Glucuronates / Mannose Limits: Humans Language: English Journal: Int J Biol Macromol Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Polysaccharides / Coronavirus Infections / Spike Glycoprotein, Coronavirus / Glucuronates / Mannose Limits: Humans Language: English Journal: Int J Biol Macromol Year: 2020 Document Type: Article