Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir

  1. Wanchao Yin
  2. Chunyou Mao
  3. Xiaodong Luan
  4. Dan-Dan Shen
  5. Qingya Shen
  6. Haixia Su
  7. Xiaoxi Wang
  8. Fulai Zhou
  9. Wenfeng Zhao
  10. Minqi Gao
  11. Shenghai Chang
  12. Yuan-Chao Xie
  13. Guanghui Tian
  14. He-Wei Jiang
  15. Sheng-Ce Tao
  16. Jingshan Shen
  17. Yi Jiang
  18. Hualiang Jiang
  19. Yechun Xu
  20. Shuyang Zhang
  21. Yan Zhang
  22. H. Eric Xu

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Abstract

Understanding the inner workings of the virus that causes coronavirus disease 2019 (COVID-19) may help us to disrupt it. Yin et al. focused on the viral polymerase essential for replicating viral RNA. They determined a structure of the polymerase bound to RNA and to the drug remdesivir. Remdesivir mimics an RNA nucleotide building block and is covalently linked to the replicating RNA, which blocks further synthesis of RNA. The structure provides a template for designing improved therapeutics against the viral polymerase.

Science , this issue p. 1499

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  1. Version published to 10.1126/science.abc1560
  2. ScreenIT

    SciScore for 10.1101/2020.04.08.032763: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Image processing and 3D reconstruction of the template and Remdesivir bound complex: Contrast transfer function parameters for each micrograph were determined by Gctf v1.06(37) and particle selection were performed using auto-picking command in RELION-3.0-beta2(38), yielding 2,438,446 particle projections.
    Gctf
    suggested: (GCTF, RRID:SCR_016500)
    This subset of particle projections was subjected to two rounds of Hetero Refinement and two selected subsets containing 580,293 projections were used to obtain a map with resolution of 2.9 Å in cryoSPARC.
    cryoSPARC
    suggested: (cryoSPARC, RRID:SCR_016501)
    Local resolution was determined using the Bsoft package with half maps as input maps(40).
    Bsoft
    suggested: (Bsoft, RRID:SCR_016503)
    The model statistics was validated using MolProbity.
    MolProbity
    suggested: (MolProbity, RRID:SCR_014226)
    Structural figures were prepared in Chimera and PyMOL (https://pymol.org/2/).
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 27 and 21. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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  3. Version published to 10.1101/2020.04.08.032763v2 on bioRxiv
  4. Version published to 10.1101/2020.04.08.032763v1 on bioRxiv