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Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir
文献类型:期刊论文
作者 | Yin, Wanchao2,3,4; Mao, Chunyou3,4; Luan, Xiaodong1,5,6,7; Shen, Dan-Dan3,4; Shen, Qingya3,4; Su, Haixia8; Wang, Xiaoxi2; Zhou, Fulai2; Zhao, Wenfeng2; Gao, Minqi9 |
刊名 | SCIENCE
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出版日期 | 2020-06-26 |
卷号 | 368期号:6498页码:1499-+ |
ISSN号 | 0036-8075 |
DOI | 10.1126/science.abc1560 |
通讯作者 | Xu, Yechun(ycxu@simm.ac.cn) ; Zhang, Shuyang(shuyangzhang103@nrdrs.org) ; Zhang, Yan(zhang_yan@zju.edu.cn) ; Xu, H. Eric(eric.xu@simm.ac.cn) |
英文摘要 | The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global crisis. Replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp) enzyme, a target of the antiviral drug remdesivir. Here we report the cryo-electron microscopy structure of the SARS-CoV-2 RdRp, both in the apo form at 2.8-angstrom resolution and in complex with a 50-base template-primer RNA and remdesivir at 2.5-angstrom resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp, where remdesivir is covalently incorporated into the primer strand at the first replicated base pair, and terminates chain elongation. Our structures provide insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection. |
WOS关键词 | CRYO-EM STRUCTURE ; RESPIRATORY SYNDROME CORONAVIRUS ; REPLICATION ; PROTEIN ; DISCOVERY ; GS-5734 ; VIRUS ; NSP12 ; EBOLA |
资助项目 | National Key R&D Programs of China[2018YFA0507002] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Shanghai Municipal Science and Technology Major Project[XDB08020303] ; Zhejiang University special scientific research fund for COVID-19 prevention and control[E33] ; National Science Foundation of China[81922071] ; Science and Technology Commission of Shanghai Municipal[20431900100] ; Jack Ma Foundation[2020-CMKYGG-05] ; CAMS Innovation Fund for 13th Five-Year National Science and Technology Major Project for New Drugs[2019ZX09734001-002] ; CAMS Innovation Fund for Medical Sciences[2020-I2M-CoV19-001] ; Tsinghua University-Peking University Center for Life Sciences[045-160321001] ; National Key Research and Development Program of China[2016YFA0500600] ; National Natural Science Foundation of China[31970130] ; National Natural Science Foundation of China[3167083] ; National Key R&D Program of China[2016YFA0502301] ; National Natural Science Foundation[31770796] ; National Science and Technology Major Project[2018ZX09711002] |
WOS研究方向 | Science & Technology - Other Topics |
语种 | 英语 |
WOS记录号 | WOS:000545264600046 |
出版者 | AMER ASSOC ADVANCEMENT SCIENCE |
源URL | [http://119.78.100.183/handle/2S10ELR8/291835] ![]() |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Xu, Yechun; Zhang, Shuyang; Zhang, Yan; Xu, H. Eric |
作者单位 | 1.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.Zhejiang Univ, Dept Biophys, Sir Run Run Shaw Hosp, Sch Med, Hangzhou 310058, Peoples R China 4.Zhejiang Univ, Dept Pathol, Sir Run Run Shaw Hosp, Sch Med, Hangzhou 310058, Peoples R China 5.Peking Union Med Coll, Dept Cardiol, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China 6.Chinese Acad Med Sci, Beijing 100730, Peoples R China 7.Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China 8.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 9.WuxiBiortus Biosci Co Ltd, Jiangyin 214437, Peoples R China 10.Zhejiang Univ, Ctr Cryoelectron Microscopy, Sch Med, Hangzhou 310058, Peoples R China |
推荐引用方式 GB/T 7714 | Yin, Wanchao,Mao, Chunyou,Luan, Xiaodong,et al. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir[J]. SCIENCE,2020,368(6498):1499-+. |
APA | Yin, Wanchao.,Mao, Chunyou.,Luan, Xiaodong.,Shen, Dan-Dan.,Shen, Qingya.,...&Xu, H. Eric.(2020).Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir.SCIENCE,368(6498),1499-+. |
MLA | Yin, Wanchao,et al."Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir".SCIENCE 368.6498(2020):1499-+. |
入库方式: OAI收割
来源:上海药物研究所
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