Fucoidan from Ascophyllum nodosum and Undaria pinnatifida attenuate SARS-CoV-2 infection in vitro and in vivo by suppressing ACE2 and alleviating inflammation

文献类型： 外文期刊

第一作者： Shi, Fang-Shu

作者： Shi, Fang-Shu;Xie, Yv-Hao;Li, Jin-Jun;Wang, Xin;Zhu, Li-Ying;Li, Xiao-Qiong;Shi, Fang-Shu;Xie, Yv-Hao;Li, Jin-Jun;Wang, Xin;Zhu, Li-Ying;Li, Xiao-Qiong;Shi, Fang-Shu;Huang, Yao-Wei;Shi, Fang-Shu;Yang, Yong-Le;Xu, Ling-Dong;Huang, Yao-Wei;Xie, Yv-Hao;Wang, Wei-Wei;Shen, Pei-li

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关键词： SARS-CoV-2; Fucoidan; ACE2; Cytokines; Gut microbiota

期刊名称：CARBOHYDRATE POLYMERS （ 影响因子：10.7； 五年影响因子：10.2 ）

ISSN： 0144-8617

年卷期： 2024 年 332 卷

页码：

收录情况： SCI

摘要： The global healthcare challenge posed by COVID-19 necessitates the continuous exploration for novel antiviral agents. Fucoidans have demonstrated antiviral activity. However, the underlying structure-activity mechanism responsible for the inhibitory activity of fucoidans from Ascophyllum nodosum (FUCA) and Undaria pinnatifida (FUCU) against SARS-CoV-2 remains unclear. FUCA was characterized as a homopolymer with a backbone structure of repeating (1 -* 3) and (1 -* 4) linked alpha-l-fucopyranose residues, whereas FUCU was a heteropolysaccharide composed of Fuc1-3Gal1-6 repeats. Furthermore, FUCA demonstrated significantly higher antiSARS-CoV-2 activity than FUCU (EC50: 48.66 vs 69.52 mu g/mL), suggesting the degree of branching rather than sulfate content affected the antiviral activity. Additionally, FUCA exhibited a dose -dependent inhibitory effect on ACE2, surpassing the inhibitory activity of FUCU. In vitro, both FUCA and FUCU treatments downregulated the expression of pro-inflammatory cytokines (IL -6, IFN-alpha, IFN-gamma, and TNF-alpha) and anti-inflammatory cytokines (IL -10 and IFN-B) induced by viral infection. In hamsters, FUCA demonstrated greater effectiveness in attenuating lung and gastrointestinal injury and reducing ACE2 expression, compared to FUCU. Analysis of the 16S rRNA gene sequencing revealed that only FUCU partially alleviated the gut microbiota dysbiosis caused by SARS-CoV-2. Consequently, our study provides a scientific basis for considering fucoidans as poteintial prophylactic food components against SARS-CoV-2.

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