科学家发现COVID-19新药物靶标!

2020-03-24 生物探索 生物探索

近日,传染病结构基因组中心(Center of Structural Genomics of InfectiousDiseases,CSGID)发现并分析了两个关键的SARS-CoV-2蛋白。

冠状病毒是一种包膜的、正链单链RNA病毒。近日,传染病结构基因组中心(Center of Structural Genomics of InfectiousDiseases,CSGID)发现并分析了两个关键的SARS-CoV-2蛋白——NSP16-NSP10,这是迄今为止CSGID科学家们确定的第4种SARS-CoV-2潜在药物靶点的蛋白质结构,其余3种重要的病毒复制蛋白结构分别为:nsp15内切酶、nsp3ADP核糖磷酸酶和nsp9复制酶。

SARS-CoV-2中NSP16-NSP10配合物的1.80埃分辨晶体结构来源:CSGID官网

NSP16-NSP10蛋白复合物称为RNA甲基转移酶或Mtase,根据之前的非典研究,NSP16和NSP10这两个蛋白结合后成为一个功能蛋白,它们可以修饰新冠病毒的遗传物质,以模拟人类的RNA,从而使病毒免于宿主的抗病毒防御,争取更多的时间繁殖。如果开发一种新药物能够抑制nsp 10/nsp 16,也可以使得免疫系统更快检测和根除病毒。

研究者首先设计了DNA片段以表达NSP16和NSP10两种蛋白质,随后分析蛋白结构。加州大学河滨医学院生物医学教授Adam Godzik表示,研究小组已向公众公布蛋白质结构,以供其他研究小组作药物研发。

SARS-CoV-2六聚体结构

Godzik指出,这是绘制新病毒全部蛋白结构图谱的一部分,目前直接方向是通过解决附加结构来扩大结构覆盖范围,另一研究方向是开展与潜在药物的共结晶实验,探究冠状病毒蛋白如何与药物结合,这将有助于开发得到新冠病毒的靶向药物。

原始出处:

Minasov, G., Shuvalova, L., Rosas-Lemus, M., et.al. 1.80 Angstrom Resolution Crystal Structure of NSP16 - NSP10 Complex from SARS-CoV-2. CSGID Mar 18, 2020

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    2020-03-26 zhaojie88
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