High-resolution structures of the SARS-CoV-2 2′- O -methyltransferase reveal strategies for structure-based inhibitor design

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Abstract

Crystal structures of an mRNA-capping enzyme from SARS-CoV-2 in complex with its substrates suggest targets for drug design.

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  1. SciScore for 10.1101/2020.08.03.234716: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Structure solution and refinement: The first structure of nsp16/nsp10 from SARS-CoV-2 in complex with SAM with the small unit cell was determined by Molecular Replacement with Phaser (48) from the CCP4 Suite (49) using the crystal structure of the nsp16/nsp10 heterodimer from SARS-CoV as a search model (PDB ID 3R24, (14)).
    SAM
    suggested: (SAM, RRID:SCR_010951)
    The initial solutions went through several rounds of refinement in REFMAC v.
    REFMAC
    suggested: (Refmac, RRID:SCR_014225)
    5.8.0258 (50) and manual model corrections using Coot (51).
    Coot
    suggested: (Coot, RRID:SCR_014222)
    MolProbity (54) (http://molprobity.biochem.duke.edu/) was used for monitoring the quality of the model during refinement and for the final validation of the structure.
    MolProbity
    suggested: (MolProbity, RRID:SCR_014226)
    Structural alignment: The PDB coordinates of SARS-CoV nsp16 and nsp10 were analyzed on the FATCAT (29) and PDBFlex servers (55) to perform structural and sequence alignment.
    FATCAT
    suggested: (FATCAT, RRID:SCR_014631)
    Structural alignments and structure figures were downloaded from the servers and modeled in Pymol open source V 2.1 (56).
    Pymol
    suggested: (PyMOL, RRID:SCR_000305)

    Results from OddPub: Thank you for sharing your data.


    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: We did not find any issues relating to colormaps.


    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.