SARS-CoV-2 mutations altering regulatory properties: deciphering host’s and virus’s perspectives

  1. Abul Bashar Mir Md. Khademul Islam
  2. Md. Abdullah-Al-Kamran Khan

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Abstract

Since the first recorded case of the SARS-CoV-2, it has acquired several mutations in its genome while spreading throughout the globe. However, apart from some changes in protein coding, functional importance of these mutations in disease pathophysiology are still largely unknown. In this study, we investigated the significance of these mutations both from the host’s and virus’s perspective by analyzing the host miRNA binding and virus’s internal ribosome entry site (IRES), respectively. Strikingly, we observed that due to the acquired mutations, host miRNAs bind differently compared to the reference; where few of the miRNAs lost and few gained the binding affinity for targeting the viral genome. Moreover, functional enrichment analysis suggests that targets of both of these gained and lost miRNAs might be involved in various host immune signaling pathways. Also, we sought to shed some insights on the impacts of mutations on the IRES structure of SARS-CoV-2. Remarkably, we detected that three particular mutations in the IRES can disrupt its secondary structure which can further make the virus less functional. These results could be valuable in exploring the functional importance of the mutations of SARS-CoV-2 and could provide novel insights into the differences observed different parts of the world.

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    SciScore for 10.1101/2020.06.15.150482: (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
    Then we used three different tools, namely-RNAhybrid [8], miRanda [9]
    miRanda
    suggested: (miRanda, RRID:SCR_017496)
    Target genes functional enrichment analysis: We performed the functional enrichment of the experimentally validated targets (obtained from mirTarBase database [11]) of miRNAs that can bind around the SNPs of SARS-CoV-2 using Gitools v1.8.4 [12] utilizing KEGG and Bioplanet pathway modules.
    mirTarBase
    suggested: (miRTarBase, RRID:SCR_017355)
    Gitools
    suggested: None
    KEGG
    suggested: (KEGG, RRID:SCR_012773)

    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.

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  2. Version published to 10.1101/2020.06.15.150482v1 on bioRxiv