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Cell Discov:海藻提取物比瑞德西韦更有效抑制SARS-CoV-2

2020-07-28 佚名 细胞

在对导致COVID-19的病毒的抗病毒效果的测试中,一种从食用海藻中提取的物质大大超过了目前用于对抗这种疾病的标准抗病毒药物瑞德西韦。

在对导致COVID-19的病毒的抗病毒效果的测试中,一种从食用海藻中提取的物质大大超过了目前用于对抗这种疾病的标准抗病毒药物瑞德西韦。肝素是一种常见的血液稀释剂,它是一种丧失了抗凝血性能的肝素变体,在抑制哺乳动物细胞中SARS-CoV-2感染方面与瑞德西韦的作用相同。

这项研究近日发表在Cell Discovery网站上,是最新的诱饵策略的例子。来自伦斯勒理工学院生物技术和跨学科研究中心(CBIS)的研究人员正在研发一种针对新型冠状病毒的新策略,这种病毒引发了当前的全球健康危机。该研究题为"Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro"。

SARS-CoV-2表面的刺突蛋白与人类细胞表面的一种分子--ACE-2受体结合。一旦结合,病毒就会将自己的遗传物质插入细胞,劫持细胞机器制造复制病毒。但是病毒也可以很容易地被说服锁定一个提供相似匹配的诱饵分子。中和后的病毒会被捕获并最终自然降解。

之前的研究表明,这种诱骗技术可以诱捕其他病毒,包括登革热、寨卡和A型流感病毒。

"我们正在学习如何阻止病毒感染,如果我们想迅速应对大流行病,我们将需要这些知识,"该研究的首席研究员、伦斯勒理工学院的化学和生物工程教授Jonathan Dordick说。"现实是我们没有好的抗病毒药物。为了保护我们自己不受未来大流行的影响,我们将需要一系列的方法来快速适应新出现的病毒。"

Cell Discovery的论文测试了从海藻中提取的三种不同的肝素(肝素、三磺酸肝素和一种非抗凝血低分子量肝素)和两种褐藻多糖(RPI-27和RPI-28)的抗病毒活性。这五种化合物都是被称为硫酸多糖的长链糖分子。本月早些时候发表在Antiviral Research上的一项结合研究结果表明,这种结构构象是一种有效的诱饵。

研究人员将这五种化合物分别作用于哺乳动物细胞上,进行了一项剂量反应研究,称为EC50 (EC50是抑制50%病毒感染的化合物有效浓度的缩写)。对于EC50的结果,这是在摩尔浓度给出的,一个较低的值标志着一个更有力的化合物。

RPI-27的EC50值约为83纳摩尔,而此前发表的瑞德西韦在同一哺乳动物细胞上的独立体外试验的EC50值为770纳摩尔。肝素的EC50为2.1微摩尔,约为瑞德西韦活性的三分之一;肝素的非抗凝类似物EC50为5.0微摩尔,约为瑞德西韦活性的五分之一。

另一项测试发现,即使在最高浓度的测试中,任何一种化合物都没有细胞毒性。

"我们感兴趣的是一种感染的新方法,"伦斯勒化学和化学生物学教授Robert Linhardt说,他正在与Dordick合作开发诱骗策略。"目前的想法是,COVID-19感染开始于鼻子,这两种物质中的任何一种都可能成为鼻喷雾剂的基础。如果你能简单地早期治疗感染,甚至在感染之前治疗,你就能在它进入身体之前阻止它。"

Dordick补充说,从海藻中提取的化合物"可以作为口服给药的基础,以解决潜在的胃肠道感染。"

在对SARS-CoV-2测序数据的研究中,Dordick和Linhardt发现了几个关于刺突蛋白结构的基序,这些基序有望与肝素匹配,这一结果在结合研究中得到证实。这种刺突蛋白被大量的聚糖包裹,这是一种适应,可以保护它不受人类酶的降解,并准备好与细胞表面的特定受体结合。

Dordick说:"这是一个非常复杂的机制,坦率地说,我们并不知道所有的细节,但我们正在获得更多的信息。这项研究清楚的一点是,分子越大,越适合。更成功的化合物是更大的硫酸盐多糖,提供了更多的位置,分子捕获病毒。"

基于结合研究的分子模型揭示了肝素在刺突蛋白上可以相互作用的位点,提高了类似硫酸多糖的应用前景。

CBIS主任Deepak Vashishth说:"Dordick教授和Linhardt教授的这项令人兴奋的研究是CBIS和伦斯勒其他地方正在进行的几项研究工作之一,目的是通过新的治疗方法和现有药物的再利用来应对covid19大流行的挑战。"

原始出处:

Paul S Kwon, Hanseul Oh, Seok-Joon Kwon, et al.Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro.Cell Discov. 2020 Jul 24;6:50. doi: 10.1038/s41421-020-00192-8. eCollection 2020.

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    2020-11-07 维他命
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    2020-08-20 hukaixun
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    2020-07-30 小刀医生
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    2020-07-30 yankaienglish

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