Structure of the 5’ untranslated region in SARS-CoV-2 genome and its specific recognition by innate immune system via the human oligoadenylate synthase 1 †

  1. Emmanuelle Bignon
  2. Tom Miclot
  3. Alessio Terenzi
  4. Giampaolo Barone
  5. Antonio Monari

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Abstract

2’-5’-Oligoadenylate synthetase 1 (OAS1) is one of the key enzymes driving the innate immune system response to SARS-CoV-2 infection whose activity has been related to COVID-19 severity. In particular, OAS1 is a sensor of endogenous RNA that triggers the 2’-5’ oligoadenylate/RNase L pathway in response to viral infections, ultimately activating the RNA-Lyase which cleaves endogenous and exogenous RNA impeding the viral maturation. Upon SARS-CoV-2 infection, OAS1 is responsible for the recognition of viral RNA and has been shown to possess a particularly high sensitivity for the 5’-untranslated (5’-UTR) RNA region, which is organized in a double-strand stem loop motif (SLA). Since the structure of the nucleic acid/protein complex has not been resolved, here we report its structure obtained by molecular modeling, including enhanced sampling approaches. We also pinpoint that the SL1 region enhances the interaction network with the enzyme, promoting specific hydrogen bonds, absent in normal double strand RNA fragments, hence rationalizing the high affinity for OAS1.

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  1. Version published to 10.1101/2021.12.10.472066v2 on bioRxiv
  2. Version published to 10.1039/d1cc07006a
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    SciScore for 10.1101/2021.12.10.472066: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    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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  4. Version published to 10.1101/2021.12.10.472066v1 on bioRxiv