A dual-receptor mechanism between integrins and ACE2 widens SARS-CoV-2 tissue tropism

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Abstract

In addition to the ACE2 receptor, SARS-CoV-2 binds to integrins to gain host cell entry and trigger pro-inflammatory integrin-mediated signalling cascades. Integrins, therefore, are likely candidates for a dual-receptor mechanism with ACE2 to explain the increased infectivity seen in SARS-CoV-2 models. As integrins are primarily expressed in vasculature and persistent vasculopathy is seen in COVID-19, examining the role of endothelial integrin involvement is crucial in uncovering the pathophysiology of SARS-CoV-2.

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  1. SciScore for 10.1101/2022.01.02.474028: (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
    In vitro assessment of Cilengitide inhibition of SARS-CoV-2 binding: An in vitro para-nitrophenyl phosphate binding assay was performed using human colorectal adenocarcinoma Caco-2 cells and formaldehyde-fixed SARS-CoV-2 to investigate the ability of RGD cyclic pentapeptide compound Cilengitide (0.05 and 0.005 μM) to reduce viral adherence, as described previously18.
    Caco-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Structures were energetically repaired in Yasara using the FoldX suite and visually compared using PyMol and CCG Molecular Operating Environment (MOE).
    FoldX
    suggested: (FoldX, RRID:SCR_008522)
    PyMol
    suggested: (PyMOL, RRID:SCR_000305)
    Only the best ranked binding pose obtained from AutoDock Vina was used for MD simulations.
    AutoDock
    suggested: (AutoDock, RRID:SCR_012746)

    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: 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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.


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