An in silico map of the SARS-CoV-2 RNA Structurome

  1. Ryan J. Andrews
  2. Jake M. Peterson
  3. Hafeez S. Haniff
  4. Jonathan Chen
  5. Christopher Williams
  6. Maison Grefe
  7. Matthew D. Disney
  8. Walter N. Moss

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Abstract

SARS-CoV-2 is a positive-sense single-stranded RNA virus that has exploded throughout the global human population. This pandemic coronavirus strain has taken scientists and public health researchers by surprise and knowledge of its basic biology (e.g. structure/function relationships in its genomic, messenger and template RNAs) and modes for therapeutic intervention lag behind that of other human pathogens. In this report we used a recently-developed bioinformatics approach, ScanFold, to deduce the RNA structural landscape of the SARS-CoV-2 transcriptome. We recapitulate known elements of RNA structure and provide a model for the folding of an essential frameshift signal. Our results find that the SARS-CoV-2 is greatly enriched in unusually stable and likely evolutionarily ordered RNA structure, which provides a huge reservoir of potential drug targets for RNA-binding small molecules. Our results also predict regions that are accessible for intermolecular interactions, which can aid in the design of antisense therapeutics. All results are made available via a public database (the RNAStructuromeDB) where they may hopefully drive drug discovery efforts to inhibit SARS-CoV-2 pathogenesis.

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    SciScore for 10.1101/2020.04.17.045161: (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
    SentencesResources
    For comparisons made between the Sarbecovirus genomes, the SARS-CoV genome (NC_004718.3) was aligned to SARS-CoV-2 (NC_045512.2) using the MAFFT webserver28 with default settings (in this case the FFT-ns-i method13 was implemented) CONCLUSION This work lays out the predicted local RNA folding landscape of the SARS-CoV-2 transcriptome.
    MAFFT
    suggested: (MAFFT, SCR_011811)
    The MFE and z-score are depicted using a 120 nt moving averages of values, raw values can be seen in Table S1. b) Overall distribution of raw z-score values calculated across the genome are shown alongside two other positive strand RNA genomes, ZIKV and HIV-1, which were analyzed using the same parameters as SARSCoV-2. c) Generic model of the first four stem loops found in the 5 UTR of Betacoronavirus genomes7,18(based on the Rfam entry for SL1-2; RF02910). d) Generi model showing the general architecture of the frameshift element (FSE) found in the similar coronavirus genomes11 (based on Rfam entry RF00507).
    Rfam
    suggested: (Rfam, SCR_007891)

    Results from OddPub: Thank you for sharing your data.

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  2. Version published to 10.1101/2020.04.17.045161 on bioRxiv