A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

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Abstract

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  1. SciScore for 10.1101/2020.03.22.002386: (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

    Experimental Models: Cell Lines
    SentencesResources
    While the cells used for these AP-MS experiments, HEK-293T kidney cells, are permissive to SARS-CoV-2 infection31, they do not represent the primary physiological site of infection.
    HEK-293T
    suggested: None
    These data support the hypothesis that SARS-CoV-2 preferentially hijacks proteins available in lung tissue and the degree of tissue specific expression may facilitate the drug targeting of host factors with fewer systemic side-effects; this observation is particularly compelling given its derivation from HEK293 cells, which are themselves not lung derived.
    HEK293
    suggested: CLS Cat# 300192/p777_HEK293, CVCL_0045
    For each affinity purification, ten million HEK293T cells were plated per 15-cm dish and transfected with up to 15 μg of individual Strep-tagged expression constructs after 20-24 hours.
    HEK293T
    suggested: None
    Software and Algorithms
    SentencesResources
    However, they differ in their complement of 3’ open reading frames: SARS-CoV-2 possesses an Orf3b and Orf10 with limited detectable protein homology to SARS-CoV16, and its Orf8 is intact while SARS-CoV encodes Orf8a and Orf8b (Fig. 1b)1,16,18.
    SARS-CoV-2
    suggested: (Sino Biological Cat# 40143-R019, AB_2827973)
    In accordance to this, when compared to overall RefSeq gene expression in the lung (median=3.198 TPM), the interacting proteins were more highly expressed (median=25.52 TPM, p=0.0007; t-test, Extended Data Fig. 4) and were also specifically enriched in lung expression relative to other tissues (Extended Data Fig. 5).
    RefSeq
    suggested: (RefSeq, SCR_003496)
    First, a 75 min acquisition, in which peptides were directly injected via a Easy-nLC 1200 (Thermo) into a Q-Exactive Plus mass spectrometer (Thermo), with all MS1 and MS2 spectra collected in the orbitrap.
    Thermo
    suggested: (Thermo Xcalibur, SCR_014593)
    Detected peptides and proteins were filtered to 1% false discovery rate in MaxQuant, and identified proteins were then subjected to protein-protein interaction scoring with both SAINTexpress20 and MiST19,97.
    MaxQuant
    suggested: (MaxQuant, SCR_014485)
          <div style="margin-bottom:8px">
            <div><b>SAINTexpress20</b></div>
            <div>suggested: None</div>
          </div>
        </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">All mass spectrometry raw data and search results files have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD018117101,102.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
          <div style="margin-bottom:8px">
            <div><b>PRIDE</b></div>
            <div>suggested: (Pride-asap, <a href="https://scicrunch.org/resources/Any/search?q=SCR_012052">SCR_012052</a>)</div>
          </div>
        </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">The over-representation analysis (ORA) was performed using the enricher function of clusterProfiler package in R with default parameters.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
          <div style="margin-bottom:8px">
            <div><b>clusterProfiler</b></div>
            <div>suggested: (clusterProfiler, <a href="https://scicrunch.org/resources/Any/search?q=SCR_016884">SCR_016884</a>)</div>
          </div>
        </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">The model was visualized in PyMOL (The PyMOL Molecular Graphics System, Version 2.3.4 Schrödinger, LLC.).</td><td style="min-width:100px;border-bottom:1px solid lightgray">
          <div style="margin-bottom:8px">
            <div><b>PyMOL</b></div>
            <div>suggested: (PyMOL, <a href="https://scicrunch.org/resources/Any/search?q=SCR_000305">SCR_000305</a>)</div>
          </div>
        </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Protein E was structurally aligned to the histone subunits using Pymol’s “align” function (https://pymolwiki.org/index.php/Align).</td><td style="min-width:100px;border-bottom:1px solid lightgray">
          <div style="margin-bottom:8px">
            <div><b>Pymol’s</b></div>
            <div>suggested: None</div>
          </div>
        </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">For both approaches, molecules were prioritized on their FDA approval status, activity at the target of interest better than 1 μM, and commercial availability, drawing on the ZINC database108.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
          <div style="margin-bottom:8px">
            <div><b>ZINC</b></div>
            <div>suggested: (Zinc, <a href="https://scicrunch.org/resources/Any/search?q=SCR_008596">SCR_008596</a>)</div>
          </div>
        </td></tr></table>
    

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