Structure of the RNA-dependent RNA polymerase from COVID-19 virus

Yan Gao; Liming Yan; Yucen Huang; Fengjiang Liu; Yao Zhao; Lin Cao; Tao Wang; Qianqian Sun; Zhenhua Ming; Lianqi Zhang; Ji Ge; Litao Zheng; Ying Zhang; Haofeng Wang; Yan Zhu; Chen Zhu; Tianyu Hu; Tian Hua; Bing Zhang; Xiuna Yang; Jun Li; Haitao Yang; Zhijie Liu; Wenqing Xu; Luke W. Guddat; Quan Wang; Zhiyong Lou; Zihe Rao

doi:10.1126/science.abb7498

Structure of the RNA-dependent RNA polymerase from COVID-19 virus

Yan Gao, Liming Yan, Yucen Huang, Fengjiang Liu, Yao Zhao, Lin Cao, Tao Wang, Qianqian Sun, Zhenhua Ming, Lianqi Zhang, Ji Ge, Litao Zheng, Ying Zhang, Haofeng Wang, Yan Zhu, Chen Zhu, Tianyu Hu, Tian Hua, Bing Zhang, Xiuna YangJun Li, Haitao Yang, Zhijie Liu, Wenqing Xu, Luke W. Guddat, Quan Wang, Zhiyong Lou, Zihe Rao

Research output: Contribution to journal › Article › peer-review

1209 Citations (Scopus)

Abstract

A novel coronavirus [severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2)] outbreak has caused a global coronavirus disease 2019 (COVID-19) pandemic, resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase [(RdRp), also named nsp12] is the central component of coronaviral replication and transcription machinery, and it appears to be a primary target for the antiviral drug remdesivir. We report the cryo–electron microscopy structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-angstrom resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified b-hairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics that target viral RdRp.

Original language	English
Pages (from-to)	779-782
Number of pages	4
Journal	Science
Volume	368
Issue number	6492
DOIs	https://doi.org/10.1126/science.abb7498
Publication status	Published - May 15 2020
Externally published	Yes

Bibliographical note

Funding Information:
care and support of our research team to enable us to carry out this research in a safe and healthy environment. It would have been impossible for us to attain this achievement without their tremendous efforts in the last 2 months during the COVID-19 pandemic. We also would like to convey our special thanks to Tsinghua University for their exceptional permission to allow five of Z.R.’s students to go back to the laboratory to prepare the protein samples for this study. We also must express our gratitude to the campus service team of ShanghaiTech University scientific research platform of Shanghai Institute for Advanced Immunochemical Studies (SIAIS), and National Center for Protein Science Shanghai (NCPSS), as well as all the manager and technician individuals those who provided onsite or remote technical support. Their kind help and fearless support are pivotal to this work during the epidemic. We would like to thank the University of Queensland and Diamond Light Source for their collaboration. Funding: This work was supported by the National Program on Key Research Project of China (grant nos. 2017YFC0840300 and 2020YFA0707500), the Strategic Priority Research Program of the Chinese Academy of Sciences (grant XDB08020200), the National Natural Science Foundation of China (grant nos. 81520108019 and 813300237), and the Science and Technology Commission of Shanghai Municipality We especially thank ShanghaiTech University and their administrative team as well as the Bio-Electron Microscopy Facility for their great

Publisher Copyright:
Copyright © 2020 The Authors,

ASJC Scopus Subject Areas

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Gao, Y, Yan, L, Huang, Y, Liu, F, Zhao, Y, Cao, L, Wang, T, Sun, Q, Ming, Z, Zhang, L, Ge, J, Zheng, L, Zhang, Y, Wang, H, Zhu, Y, Zhu, C, Hu, T, Hua, T, Zhang, B, Yang, X, Li, J, Yang, H, Liu, Z, Xu, W, Guddat, LW, Wang, Q, Lou, Z & Rao, Z 2020, 'Structure of the RNA-dependent RNA polymerase from COVID-19 virus', Science, vol. 368, no. 6492, pp. 779-782. https://doi.org/10.1126/science.abb7498

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abstract = "A novel coronavirus [severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2)] outbreak has caused a global coronavirus disease 2019 (COVID-19) pandemic, resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase [(RdRp), also named nsp12] is the central component of coronaviral replication and transcription machinery, and it appears to be a primary target for the antiviral drug remdesivir. We report the cryo–electron microscopy structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-angstrom resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified b-hairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics that target viral RdRp.",

author = "Yan Gao and Liming Yan and Yucen Huang and Fengjiang Liu and Yao Zhao and Lin Cao and Tao Wang and Qianqian Sun and Zhenhua Ming and Lianqi Zhang and Ji Ge and Litao Zheng and Ying Zhang and Haofeng Wang and Yan Zhu and Chen Zhu and Tianyu Hu and Tian Hua and Bing Zhang and Xiuna Yang and Jun Li and Haitao Yang and Zhijie Liu and Wenqing Xu and Guddat, {Luke W.} and Quan Wang and Zhiyong Lou and Zihe Rao",

note = "Funding Information: care and support of our research team to enable us to carry out this research in a safe and healthy environment. It would have been impossible for us to attain this achievement without their tremendous efforts in the last 2 months during the COVID-19 pandemic. We also would like to convey our special thanks to Tsinghua University for their exceptional permission to allow five of Z.R.{\textquoteright}s students to go back to the laboratory to prepare the protein samples for this study. We also must express our gratitude to the campus service team of ShanghaiTech University scientific research platform of Shanghai Institute for Advanced Immunochemical Studies (SIAIS), and National Center for Protein Science Shanghai (NCPSS), as well as all the manager and technician individuals those who provided onsite or remote technical support. Their kind help and fearless support are pivotal to this work during the epidemic. We would like to thank the University of Queensland and Diamond Light Source for their collaboration. Funding: This work was supported by the National Program on Key Research Project of China (grant nos. 2017YFC0840300 and 2020YFA0707500), the Strategic Priority Research Program of the Chinese Academy of Sciences (grant XDB08020200), the National Natural Science Foundation of China (grant nos. 81520108019 and 813300237), and the Science and Technology Commission of Shanghai Municipality We especially thank ShanghaiTech University and their administrative team as well as the Bio-Electron Microscopy Facility for their great Publisher Copyright: Copyright {\textcopyright} 2020 The Authors,",

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doi = "10.1126/science.abb7498",

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volume = "368",

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AU - Gao, Yan

AU - Yan, Liming

AU - Huang, Yucen

AU - Liu, Fengjiang

AU - Zhao, Yao

AU - Cao, Lin

AU - Wang, Tao

AU - Sun, Qianqian

AU - Ming, Zhenhua

AU - Zhang, Lianqi

AU - Ge, Ji

AU - Zheng, Litao

AU - Zhang, Ying

AU - Wang, Haofeng

AU - Zhu, Yan

AU - Zhu, Chen

AU - Hu, Tianyu

AU - Hua, Tian

AU - Zhang, Bing

AU - Yang, Xiuna

AU - Li, Jun

AU - Yang, Haitao

AU - Liu, Zhijie

AU - Xu, Wenqing

AU - Guddat, Luke W.

AU - Wang, Quan

AU - Lou, Zhiyong

AU - Rao, Zihe

N1 - Funding Information: care and support of our research team to enable us to carry out this research in a safe and healthy environment. It would have been impossible for us to attain this achievement without their tremendous efforts in the last 2 months during the COVID-19 pandemic. We also would like to convey our special thanks to Tsinghua University for their exceptional permission to allow five of Z.R.’s students to go back to the laboratory to prepare the protein samples for this study. We also must express our gratitude to the campus service team of ShanghaiTech University scientific research platform of Shanghai Institute for Advanced Immunochemical Studies (SIAIS), and National Center for Protein Science Shanghai (NCPSS), as well as all the manager and technician individuals those who provided onsite or remote technical support. Their kind help and fearless support are pivotal to this work during the epidemic. We would like to thank the University of Queensland and Diamond Light Source for their collaboration. Funding: This work was supported by the National Program on Key Research Project of China (grant nos. 2017YFC0840300 and 2020YFA0707500), the Strategic Priority Research Program of the Chinese Academy of Sciences (grant XDB08020200), the National Natural Science Foundation of China (grant nos. 81520108019 and 813300237), and the Science and Technology Commission of Shanghai Municipality We especially thank ShanghaiTech University and their administrative team as well as the Bio-Electron Microscopy Facility for their great Publisher Copyright: Copyright © 2020 The Authors,

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Structure of the RNA-dependent RNA polymerase from COVID-19 virus

Abstract

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