Computational search of hybrid human/ SARS-CoV-2 dsRNA reveals unique viral sequences that diverge from those of other coronavirus strains

  1. Claude Pasquier
  2. Alain Robichon

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Abstract

The role of the RNAi/Dicer/Ago system to degrade RNA viruses has been elusive in mammals, which prompted authors to think that interferon (IFN) synthesis is essential in this clade relegating the RNAi defense strategy against viral infection as accessory function. We explore the theoretical possibilities that RNAi triggered by SARS-CoV-2 might degrade some host transcripts in the opposite direction although this hypothesis seems counter intuitive. SARS-CoV-2 genome was therefore computational searched for exact intra pairing within the viral RNA and also hybrid exact pairing with human transcriptome over a minimum 20 bases length. Minimal segments of 20 bases length of SARS-CoV-2 RNA were found based on the theoretical matching with existing complementary strands in the human host transcriptome. Few human genes potentially annealing with SARS-CoV-2 RNA, among them mitochondrial deubiquitinase USP30, a subunit of ubiquitin protein ligase complex FBXO21 along with two long coding RNAs were retrieved. The hypothesis that viral originated RNAi might mediate degradation of messengers of the host transcriptome was corroborated by clinical observation and phylogenetic comparative analysis indicating a strong specificity of these hybrid pairing sequences for both SARS-CoV-2 and human genomes.

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  1. Version published to 10.1101/2020.04.08.031856v4 on bioRxiv
  2. Version published to 10.1016/j.heliyon.2021.e07284
  3. Version published to 10.1101/2020.04.08.031856v3 on bioRxiv
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    SciScore for 10.1101/2020.04.08.031856: (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
    Human transcriptome: RNA products annotated on the Genome Reference Consortium Human Build 38 patch release 13 (GRCh38.p13) were downloaded from NCBI FTP site (RefSeq accession: GCF_000001405.39).
    RefSeq
    suggested: (RefSeq, RRID:SCR_003496)
    The potential pairing were computed by aligning short 15-base sequences on RNA sequences with the STAR RNA-seq aligner [35] and by retaining only perfect matches for which the short sequence was reverse complemented.
    STAR
    suggested: (STAR, RRID:SCR_015899)
    Assesment of the scope of hybrid duplexing against other species or viruses: To assess whether the sequences identified in SARS-CoV-2 could impact other species, we used BLAST to calculate the similarities between each human sequence and the following 12 other species : Gorilla gorilla, Pan troglodytes, Pongo abelii, Papio anubis, Macaca mulatta, Sapajus apella, Mus musculus, Rattus norvegicus, Pteropus vampyrus,
    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: 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.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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  5. Version published to 10.1101/2020.04.08.031856v2 on bioRxiv
  6. Version published to 10.1101/2020.04.08.031856v1 on bioRxiv