Mutation in position of 32 (G>U) of S2M differentiate human SARS-CoV2 from Bat Coronavirus

  1. Majid Vahed
  2. Mohammad Vahed
  3. Aaron Sweeney
  4. Farshad H Shirazi
  5. Mehdi Mirsaeidi

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Abstract

The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a zoonotic pathogen that has rapidly mutated and become transmissible to humans. There is little existing data on the mutations in SARS-CoV-2 and the impact of these polymorphisms on its transmission and viral load. In this study, the SARS-CoV-2 genomic sequence was analyzed to identify variants within the 3’UTR region of its cis-regulatory RNA elements. A 43-nucleotide genetic element with a highly conserved stem-loop II-like motif (S2M), was discovered. The research revealed 32 G>U and 16 G>U/A mutations located within the S2M sequence in human SARS-CoV-2 models. These polymorphisms appear to make the S2M secondary and tertiary structures in human SARS-CoV-2 models less stable when compared to the S2M structures of bat/pangolin models. This grants the RNA structures more flexibility, which could be one of its escape mechanisms from host defenses or facilitate its entry into host proteins and enzymes. While this S2M sequence may not be omnipresent across all human SARS-CoV-2 models, when present, its sequence is always highly conserved. It may be used as a potential target for the development of vaccines and therapeutic agents.

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    SciScore for 10.1101/2020.09.02.280529: (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
    Identifying functional RNA motifs and elements was performed using RegRNA 2.0 tools (filtered to human settings) (7).
    RegRNA
    suggested: (RegRNA, RRID:SCR_013207)
    This profile was used to search for all viral sequences in GenBank, while using different combinations of 32 G>U and 16 G>U/A nucleotide substitutions that occur in a conserved region within 3’ UTR, known as the S2M motif. 2.2. Quantifying Similarities between Motifs and Structures: RNA sequences were aligned using 3’UTR (29,543–29,903), with queries in a BLASTn search of the NCBI database for S2M motifs(8, 9).
    BLASTn
    suggested: (BLASTN, RRID:SCR_001598)
    All of the structures were visualized by PyMOL (11) and analysis was performed as presented in previous studies (12, 13).
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)
    Clustal Omega was used to apply mBed algorithms for guide trees.
    Clustal Omega
    suggested: (Clustal Omega, RRID:SCR_001591)
    ClustalW alignment tools were used to execute multiple sequence alignments (16).
    ClustalW
    suggested: (ClustalW, RRID:SCR_017277)
    The S2M motifs were screened with miRBase tools in order to identify potential miRNA binding sites (17). 2.3. Identification of Single Nucleotide Substitutions in the SARS-CoV-2 Genome: Only alignment positions which harbored defined A/T/G/C residues in 95% of their genomes were considered for nucleotide substitutions (18).
    miRBase
    suggested: (miRBase, RRID:SCR_017497)
    In order to be graphically represented, sequence logos of the selected S2M motifs were then constructed using WEBLOGO (19–21).
    WEBLOGO
    suggested: (WEBLOGO, RRID:SCR_010236)
    A nucleotide BLAST search of these sequence motifs was performed on the NCBI portal.
    BLAST
    suggested: (BLASTX, RRID:SCR_001653)

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 14. 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 10.1101/2020.09.02.280529v2 on bioRxiv
  3. Version published to 10.1101/2020.09.02.280529v1 on bioRxiv