关键词: 1-Cyclo-hexyl-3-(2-mopholinoethyl) carbodiimidemetho-p-toluenesulfonate 3CL protease Acetone Alginate Angiotensin converting enzyme 2 (ACE2) COVID-19 Deuterium oxide Dimethyl sulfoxide Ecklonia kurome Okam Fucan Guluronic acid Heparan sulfate Mannuronic acid Polysaccharide SARS-CoV-2 Sodium borohydride

Mesh : Polysaccharides / pharmacology chemistry isolation & purification SARS-CoV-2 / drug effects Antiviral Agents / pharmacology chemistry isolation & purification Humans Phaeophyceae / chemistry COVID-19 Drug Treatment COVID-19 / virology Coronavirus 3C Proteases / antagonists & inhibitors metabolism chemistry Chlorocebus aethiops Vero Cells Animals Spike Glycoprotein, Coronavirus / metabolism chemistry Seaweed / chemistry Angiotensin-Converting Enzyme 2 / metabolism Alginates / chemistry pharmacology

来  源:   DOI:10.1016/j.carbpol.2021.118779   PDF(Pubmed)

Abstract:
Previous researches suggested that polysaccharides from brown algae had anti-virus activity. We hypothesized that nature polysaccharide from marine plants might have the effect on anti-SARS-CoV-2 activity. By high throughput screening to target 3CLpro enzyme using polysaccharides library, we discover a crude polysaccharide 375 from seaweed Ecklonia kurome blocked 3CLpro enzymatic activity and shows good anti-SARS-CoV-2 infection activity in cell. Further, we show that homogeneous polysaccharide 37502 from the 375 may bind to 3CLpro well and disturb spike protein binding to ACE2 receptor. The structure characterization uncovers that 37502 is alginate. These results imply that the bioactivities of 375 on SARS-CoV-2 may target multiple key molecules implicated in the virus infection and replication. The above results suggest that 375 may be a potential drug candidate against SARS-CoV-2.
摘要:
先前的研究表明,褐藻多糖具有抗病毒活性。我们假设来自海洋植物的天然多糖可能对抗SARS-CoV-2活性有影响。利用多糖文库通过高通量筛选靶向3CLpro酶,我们发现来自海藻Eckloniakurome的粗多糖375阻断了3CLpro酶活性,并在细胞中显示出良好的抗SARS-CoV-2感染活性。Further,我们显示来自375的均质多糖37502可能与3CLpro良好结合并干扰刺突蛋白与ACE2受体的结合。结构表征揭示37502是藻酸盐。这些结果表明,375对SARS-CoV-2的生物活性可能靶向涉及病毒感染和复制的多个关键分子。以上结果表明375可能是抗SARS-CoV-2的潜在候选药物。
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