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Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors

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  • Robert N. Kirchdoerfer

    (The Scripps Research Institute)

  • Andrew B. Ward

    (The Scripps Research Institute)

Abstract

Recent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 Å resolution structure of the SARS-CoV nsp12 polymerase bound to its essential co-factors, nsp7 and nsp8, using single particle cryo-electron microscopy. nsp12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is bound by two nsp8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into nsp12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.

Suggested Citation

  • Robert N. Kirchdoerfer & Andrew B. Ward, 2019. "Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10280-3
    DOI: 10.1038/s41467-019-10280-3
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    Cited by:

    1. Aijing Feng & Sarah Bevins & Jeff Chandler & Thomas J. DeLiberto & Ria Ghai & Kristina Lantz & Julianna Lenoch & Adam Retchless & Susan Shriner & Cynthia Y. Tang & Suxiang Sue Tong & Mia Torchetti & A, 2023. "Transmission of SARS-CoV-2 in free-ranging white-tailed deer in the United States," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Hafiza Salaha Mahrosh & Ghulam Mustafa, 2021. "An in silico approach to target RNA-dependent RNA polymerase of COVID-19 with naturally occurring phytochemicals," Environment, Development and Sustainability: A Multidisciplinary Approach to the Theory and Practice of Sustainable Development, Springer, vol. 23(11), pages 16674-16687, November.
    3. Xuan Zou & Xiaohong Xiao & Ziran Mo & Yashi Ge & Xing Jiang & Ruolin Huang & Mengxue Li & Zixin Deng & Shi Chen & Lianrong Wang & Sang Yup Lee, 2022. "Systematic strategies for developing phage resistant Escherichia coli strains," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Hari Vishal Lakhani & Sneha S. Pillai & Mishghan Zehra & Ishita Sharma & Komal Sodhi, 2020. "Systematic Review of Clinical Insights into Novel Coronavirus (CoVID-19) Pandemic: Persisting Challenges in U.S. Rural Population," IJERPH, MDPI, vol. 17(12), pages 1-14, June.
    5. Mohamed Fareh & Wei Zhao & Wenxin Hu & Joshua M. L. Casan & Amit Kumar & Jori Symons & Jennifer M. Zerbato & Danielle Fong & Ilia Voskoboinik & Paul G. Ekert & Rajeev Rudraraju & Damian F. J. Purcell , 2021. "Reprogrammed CRISPR-Cas13b suppresses SARS-CoV-2 replication and circumvents its mutational escape through mismatch tolerance," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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