In silico analyses on the comparative sensing of SARS‐CoV‐2 mRNA by the intracellular TLRs of humans
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Abstract
The coronavirus disease‐2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has already resulted in a huge setback to mankind in terms of millions of deaths, while the unavailability of an appropriate therapeutic strategy has made the scenario much more severe. Toll‐like receptors (TLRs) are crucial mediators and regulators of host immunity and the role of human cell surface TLRs in SARS‐CoV‐2 induced inflammatory pathogenesis has been demonstrated recently. However, the functional significance of the human intracellular TLRs including TLR3, 7, 8, and 9 is yet unclear. Hitherto, the involvement of these intracellular TLRs in inducing pro‐inflammatory responses in COVID‐19 has been reported but the identity of the interacting viral RNA molecule(s) and the corresponding TLRs have not been explored. This study hopes to rationalize the comparative binding of the major SARS‐CoV‐2 mRNAs to the intracellular TLRs, considering the solvent‐based force‐fields operational in the cytosolic aqueous microenvironment that predominantly drives these interactions. Our in silico study on the binding of all mRNAs with the intracellular TLRs depicts that the mRNA of NSP10, S2, and E proteins of SARS‐CoV‐2 are possible virus‐associated molecular patterns that bind to TLR3, TLR9, and TLR7, respectively, and trigger downstream cascade reactions. Intriguingly, binding of the viral mRNAs resulted in variable degrees of conformational changes in the ligand‐binding domain of the TLRs ratifying the activation of the downstream inflammatory signaling cascade. Taken together, the current study is the maiden report to describe the role of TLR3, 7, and 9 in COVID‐19 immunobiology and these could serve as useful targets for the conception of a therapeutic strategy against the pandemic.
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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.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources 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. ExPASysuggested: NoneTo 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. PyMOLsuggested: (PyMOL, RRID:SCR_000305)Results from OddPub: Thank you for sharing your data.
Result…SciScore for 10.1101/2020.11.11.377713: (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 Sentences Resources 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. ExPASysuggested: NoneTo 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. PyMOLsuggested: (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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