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

• Published in: Carbohydrate polymers 2024-05, Vol.332, p.121884-121884, Article 121884
• Main Authors: Shi, Fang-Shu, Xie, Yv-Hao, Yang, Yong-Le, Xu, Ling-Dong, Li, Jin-Jun, Wang, Xin, Zhu, Li-Ying, Wang, Wei-Wei, Shen, Pei-li, Huang, Yao-Wei, Li, Xiao-Qiong
• Format: Article
• Language: English
• Subjects: ACE2; Angiotensin-Converting Enzyme 2; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; antiviral properties; Ascophyllum - chemistry; Ascophyllum nodosum; COVID-19; COVID-19 infection; Cytokines; dose response; dysbiosis; Edible Seaweeds; Fucoidan; gastrointestinal system; genes; Gut microbiota; health services; Humans; Inflammation; interleukin-10; interleukin-6; intestinal microorganisms; lungs; median effective concentration; polymers; Polysaccharides; RNA, Ribosomal, 16S; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; sulfates; Undaria - chemistry; Undaria pinnatifida
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2024.121884

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 α-l-fucopyranose residues, whereas FUCU was a heteropolysaccharide composed of Fuc1–3Gal1–6 repeats. Furthermore, FUCA demonstrated significantly higher anti-SARS-CoV-2 activity than FUCU (EC50: 48.66 vs 69.52 μg/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-α, IFN-γ, and TNF-α) and anti-inflammatory cytokines (IL-10 and IFN-β) 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. [Display omitted] •The inhibitory activity of FUCA against SARS-CoV-2 was higher than that of FUCU, possibly due to the branching structure of fucoidan.•FUCA exhibited superior efficacy compared to FUCU in mitigating lung and gastrointestinal tract injuries in SARS-CoV-2-infected hamsters, which was achieved through the inhibition of ACE2 expression and subsequent inflammatory responses.