Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites

• Published in: Acta pharmaceutica Sinica. B 2020-07, Vol.10 (7), p.1228-1238
• Main Authors: Kang, Sisi, Yang, Mei, Hong, Zhongsi, Zhang, Liping, Huang, Zhaoxia, Chen, Xiaoxue, He, Suhua, Zhou, Ziliang, Zhou, Zhechong, Chen, Qiuyue, Yan, Yan, Zhang, Changsheng, Shan, Hong, Chen, Shoudeng
• Format: Article
• Language: English
• Subjects: Antiviral targeting site; Coronavirus; COVID-19; Crystal structure; Nucleocapsid protein; Original article; RNA binding domain; SARS-CoV-2
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2020.04.009

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. The crystal structure of the N-terminal RNA-binding domain of SARS-CoV-2 nucleocapsid protein was determined by X-ray. Compared with other previously reported coronavirus nucleocapsid protein N-terminal domains, the authors have identified a unique potential RNA-binding pocket that can guide the design of novel antiviral drugs targeting SARS-CoV-2. [Display omitted]