國家衛生研究院 NHRI:Item 3990099045/15175

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15175

Title:	Natural fucoidans inhibit coronaviruses by targeting viral spike protein and host cell furin
Authors:	Yang, CW;Hsu, HY;Lee, YZ;Jan, JT;Chang, SY;Lin, YL;Yang, RB;Chao, TL;Liang, JJ;Lin, SJ;Liao, CC;Chang, CS;Sytwu, HK;Hung, MS;Chen, CT;Lee, SJ
Contributors:	Institute of Biotechnology and Pharmaceutical Research;National Institute of Infectious Diseases and Vaccinology
Abstract:	Fucoidans are a class of long chain sulfated polysaccharides and have multiple biological functions. Herein, four natural fucoidans extracted from Fucus vesiculosus, F. serratus, Laminaria japonica and Undaria pinnatifida, were tested for their HCoV-OC43 inhibition and found to demonstrate EC(50) values ranging from 0.15 to 0.61 µg/mL. That from U. pinnatifida exhibited the most potent anti-HCoV-OC43 activity with an EC(50) value of 0.15 ± 0.02 µg/mL, a potency largely independent of its sulfate content. Comparison of the gene expression profiles of fucoidan-treated and untreated cells infected with HCoV-OC43 revealed that fucoidan treatment effectively diminished HCoV-OC43 gene expressions associated with induced chemokines, cytokines and viral activities. Further studies using a highly fucoidan-resistant HCoV-OC43 determined that fucoidan inhibited HCoV-OC43 infection via interfering with viral entry and led to the identification of the specific site on the N-terminal region of spike protein, that located adjacent to the host cell receptor binding domain, targeted by the virus. Furthermore, in a SARS-CoV-2 pseudovirus neutralization assay, fucoidan also blocked SARS-CoV-2 entry. In vitro and in vivo, fucoidan decreased SARS-CoV-2 viral loads and inhibited viral infection in Calu-3 or Vero E 6 cells and SARS-CoV-2 infected hamsters, respectively. Fucoidan was also found to inhibit furin activity, and reported furin inhibitors were found to inhibit viral infection by wild type HCoV-OC43 or SARS-CoV-2. Accordingly, we conclude that fucoidans inhibit coronaviral infection by targeting viral spike protein and host cell furin to interfere with viral entry.
Date:	2023-07-20
Relation:	Biochemical Pharmacology. 2023 Jul 20;215:Article number 115688.
Link to:	http://dx.doi.org/10.1016/j.bcp.2023.115688
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0006-2952&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:001047375800001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85166234927
Appears in Collections:	[Shiow-Ju Lee] Periodical Articles [Chiung-Tong Chen] Periodical Articles [Ming-Shiu Hung] Periodical Articles [Huey-Kang Sytwu] Periodical Articles

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