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

Sisi Kang; Mei Yang; Zhongsi Hong; Liping Zhang; Zhaoxia Huang; Xiaoxue Chen; Suhua He; Ziliang Zhou; Zhechong Zhou; Qiuyue Chen; Yan Yan; Changsheng Zhang; Hong Shan; Shoudeng Chen

doi:10.1016/j.apsb.2020.04.009

Acta Pharmaceutica Sinica B (Jul 2020)

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

Sisi Kang,
Mei Yang,
Zhongsi Hong,
Liping Zhang,
Zhaoxia Huang,
Xiaoxue Chen,
Suhua He,
Ziliang Zhou,
Zhechong Zhou,
Qiuyue Chen,
Yan Yan,
Changsheng Zhang,
Hong Shan,
Shoudeng Chen

Affiliations

Sisi Kang: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
Mei Yang: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
Zhongsi Hong: Department of Infectious Diseases, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
Liping Zhang: 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
Zhaoxia Huang: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
Xiaoxue Chen: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
Suhua He: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
Ziliang Zhou: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
Zhechong Zhou: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
Qiuyue Chen: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
Yan Yan: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China
Changsheng Zhang: 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
Hong Shan: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China; Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China; Department of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China; Corresponding authors. Tel: +86 13612221254 (Shoudeng Chen), +86 18207306672 (Hong Shan).
Shoudeng Chen: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China; Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China; Department of Experimental Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China; Corresponding authors. Tel: +86 13612221254 (Shoudeng Chen), +86 18207306672 (Hong Shan).

DOI: https://doi.org/10.1016/j.apsb.2020.04.009
Journal volume & issue: Vol. 10, no. 7
pp. 1228 – 1238

Abstract

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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.

Published in Acta Pharmaceutica Sinica B

ISSN: 2211-3835 (Print); 2211-3843 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.sciencedirect.com/journal/acta-pharmaceutica-sinica-b

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