论文标题
天然多酚foldunellin及其结构类似物是SARS-COV-2主蛋白酶二聚化的抑制剂，如分子模拟研究所揭示的那样
The natural polyphenol fortunellin and its structural analogs are inhibitors of the SARS-CoV-2 main proteinase dimerization, as revealed by molecular simulation studies
论文作者
论文摘要
3Cl-Pro（或M-Pro）是SARS-COV-2主要蛋白酶，用作同型二聚体，是导致作用于病毒生长和复制的蛋白质中大的多蛋白1AB转录本的切割。 3Cl-Pro是研究最多的SARS-COV-2蛋白之一，也是治疗干预措施的主题，其针对其催化域。已经报道了许多候选药物，包括一些天然产品。在这里，我们通过结合和分子动力学模拟在计算机中进行了研究，这是鉴定3Cl-Pro二聚体抑制剂候选物的自然产物空间。我们报告说，Fortunellin（Acacetin 7-O-Neohesperidoside）是一种天然类黄酮O-糖苷，是一种有效的3Cl-PRO二聚化抑制剂。对锌天然产品数据库的搜索确定了另外16个相关分子，包括丙糖蛋白和瑞氏蛋白，具有有趣的药理特性。我们建议Fortunellin及其结构类似物可能是针对SARS-COV-2诱导的Covid-19疾病的新型药物和饮食补充剂的基础。
3CL-Pro (or M-Pro) is the SARS-CoV-2 main protease, acting as a homodimer, is responsible for the cleavage of the large polyprotein 1ab transcript in proteins acting on viral growth and replication. 3CL-Pro has been one of the most studied SARS-CoV-2 proteins and the subject of therapeutic interventions, targeting its catalytic domain. A number of drug candidates have been reported, including some natural products. Here, we investigated in silico, through binding and molecular dynamics simulations, the natural product space for the identification of candidates of 3CL-Pro dimerization inhibitors. We report that fortunellin (acacetin 7-O-neohesperidoside), a natural flavonoid O-glycoside, is a potent inhibitor of 3CL-Pro dimerization. A search of the ZINC natural products database identified another 16 related molecules, including apilin and rhoifolin, with interesting pharmacological properties. We propose that fortunellin and its structural analogs might be the basis of novel pharmaceuticals and dietary supplements against SARS-CoV-2 induced COVID-19 disease.
