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 Å 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 β-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.

由 SARS-CoV-2 病毒引起的冠状病毒病（COVID-19）的爆发不断导致世界范围内的人类感染和死亡。目前，还没有特定的病毒蛋白靶向疗法。病毒核衣壳蛋白是潜在的抗病毒药物靶点，在病毒生命周期中发挥多种关键功能。然而，SARS-CoV-2核衣壳蛋白的结构信息仍不清楚。在此，我们确定了 SARS-CoV-2 核衣壳蛋白 N 末端 RNA 结合域的 2.7 Å 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势特征是不同的。与轻度病毒型 HCoV-OC43 等效结构域的进一步比较表明， β片层核心旁边有一个独特的潜在 RNA 结合袋。通过体外结合研究的补充，我们的数据提供了 SARS-CoV-2 核衣壳蛋白 N 末端结构域的几个原子分辨率特征，指导特异性针对 SARS-CoV-2 的新型抗病毒药物的设计。