Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites
Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites
复制标题
SARS-CoV-2核衣壳蛋白RNA结合域的晶体结构揭示了潜在的独特药物靶向位点
DOI：
10.1016/j.apsb.2020.04.009
复制
发表时间：
2020-07-01
影响因子：
14.5
通讯作者：
Chen, Shoudeng
中科院分区：
文献类型：
--
作者：
Kang, Sisi;Yang, Mei;Chen, Shoudeng
由SARS-CoV-2病毒引起的冠状病毒病（COVID-19）的爆发不断导致全球人类感染和死亡。目前，还没有特异性的病毒蛋白靶向治疗方法。病毒核衣壳蛋白是一种潜在的抗病毒药物靶点，在病毒生命周期中起着多种关键作用。然而，SARS-CoV-2核衣壳蛋白的结构信息尚不清楚。本文确定了SARS-CoV-2核衣壳蛋白n端RNA结合域的2.7埃晶体结构。虽然整体结构与其他报道的冠状病毒核衣壳蛋白n端结构域相似，但它们之间的表面静电电位特征不同。与轻度病毒型HCoV-OC43等效结构域的进一步比较表明，在β -sheet核心旁边有一个独特的潜在RNA结合口袋。通过体外结合研究，我们的数据提供了SARS-CoV-2核衣壳蛋白n端结构域的几个原子分辨率特征，指导了针对SARS-CoV-2的新型抗病毒药物的设计。(C) 2020年中国药学会、中国医学科学院药物研究所。制作和托管由爱思唯尔B.V.
The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 angstrom crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the beta-sheet core. Complemented by in vitro binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.