Synthesis of low-molecular weight fucoidan derivatives and their binding abilities to SARS-CoV-2 spike proteins

Tatsuki Koike, Aoi Sugimoto, Shuhei Kosono, Sumika Komaba, Yuko Kanno, Takashi Kitamura, Itsuki Anzai, Tokiko Watanabe, Daisuke Takahashi, Kazunobu Toshima

Research output: Contribution to journalArticlepeer-review

Abstract

Fucoidan derivatives10-13, whose basic sugar chains are composed of repeating α(1,4)-linkedl-fucopyranosyl residues with different sulfation patterns, were designed and systematically synthesized. A structure-activity relationship (SAR) study examined competitive inhibition by thirteen fucoidan derivatives against heparin binding to the SARS-CoV-2 spike (S) protein. The results showed for the first time that10exhibited the highest inhibitory activity of the fucoidan derivatives used. The inhibitory activity of10was much higher than that of fondaparinux, the reported ligand of SARS-CoV-2 S protein. Furthermore,10exhibited inhibitory activities against the binding of heparin with several mutant SARS-CoV-2 S proteins, but was found to not inhibit factor Xa (FXa) activity that could otherwise lead to undesirable anticoagulant activity.

Original languageEnglish
Pages (from-to)2016-2021
Number of pages6
JournalRSC Medicinal Chemistry
Volume12
Issue number12
DOIs
Publication statusPublished - 2021 Dec

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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