COVID‐19, caused by SARS‐CoV‐2, has resulted in severe and unprecedented economic and social disruptions in the world. Nucleocapsid (N) protein, which is the major structural component of the virion and is involved in viral replication, assembly and immune regulation, plays key roles in the viral life cycle. Here, we solved the crystal structures of the N‐ and C‐terminal domains (N‐NTD and N‐CTD) of SARS‐CoV‐2 N protein, at 1.8 and 1.5 Å resolution, respectively. Both structures show conserved features from other CoV N proteins. The binding sites targeted by small molecules against HCoV‐OC43 and MERS‐CoV, which inhibit viral infection by blocking the RNA‐binding activity or normal oligomerization of N protein, are relatively conserved in our structure, indicating N protein is a promising drug target. In addition, certain areas of N‐NTD and N‐CTD display distinct charge distribution patterns in SARS‐CoV‐2, which may alter the RNA‐binding modes. The specific antigenic characteristics are critical for developing specific immune‐based rapid diagnostic tests. Our structural information can aid in the discovery and development of antiviral inhibitors against SARS‐CoV‐2 in the future.

中文翻译：

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SARS-CoV-2核衣壳的结构及其药物设计前景。

由 SARS-CoV-2 引起的 COVID-19 已在世界范围内造成了前所未有的严重经济和社会混乱。核衣壳 (N) 蛋白是病毒体的主要结构成分，参与病毒复制、组装和免疫调节，在病毒生命周期中起着关键作用。在这里，我们分别以 1.8 和 1.5 Å 的分辨率解析了 SARS-CoV-2 N 蛋白的 N 和 C 端结构域（N-NTD 和 N-CTD）的晶体结构。两种结构都显示出来自其他 CoV N 蛋白的保守特征。小分子针对 HCoV-OC43 和 MERS-CoV 的结合位点通过阻断 RNA 结合活性或 N 蛋白的正常寡聚化来抑制病毒感染，在我们的结构中相对保守，表明 N 蛋白是一个有前景的药物靶点。此外，N-NTD 和 N-CTD 的某些区域在 SARS-CoV-2 中显示出不同的电荷分布模式，这可能会改变 RNA 结合模式。特定的抗原特征对于开发特定的基于免疫的快速诊断测试至关重要。我们的结构信息可以帮助未来发现和开发针对 SARS-CoV-2 的抗病毒抑制剂。