In silico analyses on the comparative sensing of SARS-CoV-2 mRNA by intracellular TLRs of human

  1. Abhigyan Choudhury
  2. Nabarun Chandra Das
  3. Ritwik Patra
  4. Suprabhat Mukherjee

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Abstract

The worldwide outbreak of COVID-19 pandemic caused by SARS-CoV-2 leads to loss of mankind and global economic stability. The continuous spreading of the disease and its pathogenesis takes millions of lives of peoples and the unavailability of appropriate therapeutic strategy makes it much more severe. Toll-like receptors (TLRs) are the crucial mediators and regulators of host immunity. The role of several TLRs in immunomodulation of host by SARS-CoV-2 is recently demonstrated. However, the functionality of human intracellular TLRs including TLR3,7,8 and 9 is still being untested for sensing of viral RNA. This study is hoped to rationalize the comparative binding and sensing of SARS-CoV-2 mRNA towards the intracellular TLRs, considering the solvent-based force-fields operational in the cytosolic aqueous microenvironment that predominantly drive these reactions. Our in-silico study on the binding of all mRNAs with the intracellular TLRs shown that the mRNA of NSP10, S2, and E proteins of SARS-CoV-2 are potent enough to bind with TLR3, TLR9, and TLR7 and trigger downstream cascade reactions, and may be used as an option for validation of therapeutic option and immunomodulation against COVID-19.

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    SciScore for 10.1101/2020.11.11.377713: (What is this?)

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

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    Table 2: Resources

    Software and Algorithms
    SentencesResources
    However, the structures of TLR7 and TLR9 were obtained by performing homology modelling in the SWISS-MODEL server from ExPASy (https://swissmodel.expasy.org/) by using protein sequences obtained from GenBank with Accession No. AAZ99026 and AAZ95518.1 respectively.
    ExPASy
    suggested: None
    To perform further studies, PyMOL is used for removing water molecules, aboriginal heteroatoms as well as any xenobiotic ligands whenever present, and adding polar hydrogens and Kollman charges to the structures.
    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 28. 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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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  2. Version published to 10.1101/2020.11.11.377713 on bioRxiv