Research Article

虫草素作为SARS-CoV-2 RNA依赖性RNA聚合酶(RdRp)的有希望的抑制剂

卷 29, 期 1, 2022

发表于: 20 August, 2021

页: [152 - 162] 页: 11

弟呕挨: 10.2174/0929867328666210820114025

价格: $65

摘要

背景:在中国武汉出现的SARS-CoV-2是一种新的全球威胁,已经造成数百万人死亡,并将继续如此。这场大流行不仅威胁到人的生命,而且还引发了世界各地的经济衰退。研究人员在发现SARSCoV-2发病机制的分子见解和开发疫苗方面取得了重大进展,但仍然没有成功治愈SARS-CoV-2感染患者的方法。目的:本研究提出了一种药物重新定位管道,用于设计和发现一种有效的真菌衍生生物活性代谢物作为抗SARS-CoV-2的候选药物。 方法:选择真菌衍生物"虫草素"研究对SARS-CoV-2的RNA依赖性RNA聚合酶(RdRp)(PDB ID:6M71)的抑制特性。利用化学信息学方法测定了该化合物的药理学特征,分子间相互作用,结合能和稳定性。随后,进行了分子动力学模拟,以更好地了解虫草素与RdRp的结合机理。 结果:药理学资料和检索到的分子动力学模拟轨迹表明,虫草素具有优异的药物相似性和更高的结构稳定性,而RdRp的催化残基(Asp760、Asp761)以及其他活性位点残基(Trp617、Asp618、Tyr619、Trp800、Glu811)在整体模拟过程中表现出较好的稳定性。 结论:药理学研究结果及分子模拟结果显示,虫草素对SARSCoV-2聚合酶(RdRp)具有很强的抑制潜力。因此,强烈建议在实验室中测试虫草素,以确认其对SARS-CoV-2聚合酶(RdRp)的抑制潜力。

关键词: 虫草素,生物活性代谢物,药物再利用,SARS-CoV-2,COVID-19,分子动力学模拟。

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