Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2
Summary: The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has caused a huge number of human deaths. Currently, there are no specific drugs or vaccines available for this virus (SARS-CoV-2). The viral polymerase is a promising antiviral target. Here, we describe the near-atomic-reso...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720307543 |
| _version_ | 1819226977713782784 |
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| author | Qi Peng Ruchao Peng Bin Yuan Jingru Zhao Min Wang Xixi Wang Qian Wang Yan Sun Zheng Fan Jianxun Qi George F. Gao Yi Shi |
| author_facet | Qi Peng Ruchao Peng Bin Yuan Jingru Zhao Min Wang Xixi Wang Qian Wang Yan Sun Zheng Fan Jianxun Qi George F. Gao Yi Shi |
| author_sort | Qi Peng |
| collection | DOAJ |
| description | Summary: The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has caused a huge number of human deaths. Currently, there are no specific drugs or vaccines available for this virus (SARS-CoV-2). The viral polymerase is a promising antiviral target. Here, we describe the near-atomic-resolution structure of the SARS-CoV-2 polymerase complex consisting of the nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembles the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases and suggests a mechanism of activation by cofactors. Biochemical studies reveal reduced activity of the core polymerase complex and lower thermostability of individual subunits of SARS-CoV-2 compared with SARS-CoV. These findings provide important insights into RNA synthesis by coronavirus polymerase and indicate adaptation of SARS-CoV-2 toward humans with a relatively lower body temperature than the natural bat hosts. |
| first_indexed | 2024-12-23T10:34:04Z |
| format | Article |
| id | doaj.art-9a0c7ea178ea49daadf2fa1a48b9570b |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T10:34:04Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-9a0c7ea178ea49daadf2fa1a48b9570b2022-12-21T17:50:20ZengElsevierCell Reports2211-12472020-06-013111107774Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2Qi Peng0Ruchao Peng1Bin Yuan2Jingru Zhao3Min Wang4Xixi Wang5Qian Wang6Yan Sun7Zheng Fan8Jianxun Qi9George F. Gao10Yi Shi11CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, ChinaSavaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China; Center for Influenza Research and Early Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China; Center for Influenza Research and Early Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China; Center for Influenza Research and Early Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing 100101, China; Chongqing Key Laboratory of Neurodegenerative Diseases, Chongqing General Hospital, University of the Chinese Academy of Sciences, Chongqing 400013, China; College of Basic Medicine, Jilin University, Changchun, Jilin 130021, China; Corresponding authorSummary: The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has caused a huge number of human deaths. Currently, there are no specific drugs or vaccines available for this virus (SARS-CoV-2). The viral polymerase is a promising antiviral target. Here, we describe the near-atomic-resolution structure of the SARS-CoV-2 polymerase complex consisting of the nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembles the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases and suggests a mechanism of activation by cofactors. Biochemical studies reveal reduced activity of the core polymerase complex and lower thermostability of individual subunits of SARS-CoV-2 compared with SARS-CoV. These findings provide important insights into RNA synthesis by coronavirus polymerase and indicate adaptation of SARS-CoV-2 toward humans with a relatively lower body temperature than the natural bat hosts.http://www.sciencedirect.com/science/article/pii/S2211124720307543SARS-CoV-2non-structural proteinspolymerasecofactorsRNA synthesiscryo-EM |
| spellingShingle | Qi Peng Ruchao Peng Bin Yuan Jingru Zhao Min Wang Xixi Wang Qian Wang Yan Sun Zheng Fan Jianxun Qi George F. Gao Yi Shi Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2 Cell Reports SARS-CoV-2 non-structural proteins polymerase cofactors RNA synthesis cryo-EM |
| title | Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2 |
| title_full | Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2 |
| title_fullStr | Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2 |
| title_full_unstemmed | Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2 |
| title_short | Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2 |
| title_sort | structural and biochemical characterization of the nsp12 nsp7 nsp8 core polymerase complex from sars cov 2 |
| topic | SARS-CoV-2 non-structural proteins polymerase cofactors RNA synthesis cryo-EM |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720307543 |
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