Antiviral drug design based on structural insights into the N-terminal domain and C-terminal domain of the SARS-CoV-2 nucleocapsid protein

作     者：Xiaodong Luan Xinming Li Yufan Li Gengchen Su Wanchao Yin Yi Jiang Ning Xu Feng Wang Wang Cheng Ye Jin Leike Zhang H.Eric Xu Yi Xue Shuyang Zhang 栾晓东;黎欣明;李宇凡;苏庚辰;尹万超;蒋轶;徐宁;王峰;程望;金晔;张磊砢;徐华强;薛毅;张抒扬

作者机构：School of MedicineTsinghua UniversityBeijing 100084China Department of CardiologyPeking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China Tsinghua-Peking Center for Life SciencesTsinghua UniversityBeijing 100084China School of Life ScienceTsinghua UniversityBeijing 100084China Beijing Advanced Innovation Center for Structural BiologyBeijing 100084China The CAS Key Laboratory of Receptor ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of SciencesBeijing 100049China WuxiBiortus Biosciences Co.Ltd.Jiangyin 214437China State Key Laboratory of VirologyWuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China 

出 版 物：《Science Bulletin》 (科学通报（英文版）)

年 卷 期：2022年第67卷第22期

页      面：2327-2335页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：supported by Beijing Natural Science Foundation(M21016) Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-003 and 2021-CAMS-JZ004) Tsinghua-Peking Center for Life Sciences (045-61020100122) Beijing Advanced Innovation Center for Structural Biology 

主　　题：SARS-CoV-2 Nucleocapsid protein N-terminal domain Ceftriaxone sodium 

摘      要：Nucleocapsid(N) protein plays crucial roles in the life cycle of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), including the formation of ribonucleoprotein(RNP) complex with the viral *** we reported the crystal structures of the N-terminal domain(NTD) and C-terminal domain(CTD) of the N protein and an NTD-RNA complex. Our structures reveal a unique tetramer organization of NTD and identify a distinct RNA binding mode in the NTD-RNA complex, which could contribute to the formation of the RNP complex. We also screened small molecule inhibitors of N-NTD and N-CTD and discovered that ceftriaxone sodium, an antibiotic, can block the binding of RNA to NTD and inhibit the formation of the RNP complex. These results together could facilitate the further research of antiviral drug design targeting N protein.