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

作　　者：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 

机构地区：[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 [4]Guangdong Provincial Engineering Research Center of Molecular Imaging,the Fifth Affiliated Hospital,Sun Yatsen University,Zhuhai 519000,China [5]Department of Interventional Medicine,the Fifth Affiliated Hospital,Sun Yat-sen University,Zhuhai 519000,China [6]Department of Experimental Medicine,the Fifth Affiliated Hospital,Sun Yat-sen University,Zhuhai 519000,China

出　　处：《Acta Pharmaceutica Sinica B》2020年第7期1228-1238,共11页药学学报（英文版）

基　　金：supported by National Natural Science Foundation of China(31770801);Special Fund for Scientific and Technological Innovation Strategy of Guangdong Province of China(2018B030306029 and 2017A030313145);National Natural Science Foundation of China(81430041,81620108017);National Key Basic Research Program,China(SQ2018YFC090075);National Natural Science Foundation of China(81870019)

摘　　要：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 A 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 theβ-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.

关 键 词：COVID-19 CORONAVIRUS SARS-CoV-2 Nucleocapsid protein RNA binding domain Crystal structure Antiviral targeting site 

分 类 号：R563.1[医药卫生—呼吸系统]