Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites.
10.1016/j.apsb.2020.04.009
- Author:
Sisi KANG
1
;
Mei YANG
1
;
Zhongsi HONG
2
;
Liping ZHANG
3
;
Zhaoxia HUANG
1
;
Xiaoxue CHEN
1
;
Suhua HE
1
;
Ziliang ZHOU
1
;
Zhechong ZHOU
1
;
Qiuyue CHEN
1
;
Yan YAN
1
;
Changsheng ZHANG
3
;
Hong SHAN
1
;
Shoudeng CHEN
1
Author Information
1. Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
2. Department of Infectious Diseases, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
3. Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Institution of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
- Publication Type:Journal Article
- Keywords:
Antiviral targeting site;
COVID-19;
Coronavirus;
Crystal structure;
Nucleocapsid protein;
RNA binding domain;
SARS-CoV-2
- From:
Acta Pharmaceutica Sinica B
2020;10(7):1228-1238
- CountryChina
- Language:English
-
Abstract:
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 -sheet core. Complemented by 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.
