Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting

  1. Ali Hosseini Rad SM
  2. Alexander D. McLellan

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Abstract

The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2 permissive host cells, we identified twelve separate target sequences in the SARS-CoV-2 genome; eight of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host could be constrained by host miRNA defence. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineered viral attenuation and antigen presentation.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.15.098947: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    SARS-CoV-2 virus reference sequence was downloaded from NCBI (NC_045512.2) along with 55 sequences up to May 1st, 2020 from NCBI or GASID databases.
    GASID
    suggested: None
    Clustal Omega and Geneious alignment tools were used to perform multiple sequence alignment.
    Clustal Omega
    suggested: (Clustal Omega, RRID:SCR_001591)
    Geneious
    suggested: (Geneious, RRID:SCR_010519)
    To evaluate the impact of mutations on RNA secondary setructure and base-pair probability, we utilized RNAfold, RNAalifold [43], MutaRNA [40,44] and RNAsnp [45] programs.
    RNAsnp
    suggested: (RNAsnp, RRID:SCR_010837)
    For identifying potential miRNA binding sites, the SARS-COV-2 genome was screened with RegRNA2 and miRDB [46].
    miRDB
    suggested: (miRDB, RRID:SCR_010848)
    The expression level of miRNAs in target cells were determined by TissueAtlas [49], IMOTA [50], or using published data.
    TissueAtlas
    suggested: (TissueAtlas, RRID:SCR_017352)

    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.

    About SciScore

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  2. Version published to 10.1101/2020.05.15.098947v1 on bioRxiv