In-Silico analysis reveals lower transcription efficiency of C241T variant of SARS-CoV-2 with host replication factors MADP1 and HNRNP-1

  1. Armi Chaudhari
  2. Minal Chaudhari
  3. Sapna Mahera
  4. Zuber Saiyed
  5. Neelam M. Nathani
  6. Shantanu Shukla
  7. Chirag Patel
  8. Dhaval Patel
  9. Madhvi Joshi
  10. Chaitanya G. Joshi

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Abstract

Novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has claimed more than 1.5 million lives worldwide and counting. As per the GISAID database, the genomics of SARS-CoV2 is extensively studied with more than 500 genome submissions per day. Out of several hotspot mutations within the SARS-CoV-2 genome, researchers have focused a lot on missense variants but the least work is done on the UTRs. One of the most frequent 5’ UTR variants in the SARS-CoV-2 genome is the C241T with a global frequency of more than 0.9. In the present study, the effect of the C241T mutation has been studied with respect to change in RNA structure and its interaction with the host replication factors MADP1 Zinc finger CCHC-type and RNA-binding motif 1 (hnRNP1). The results obtained from molecular docking and molecular dynamics simulation indicated weaker interaction of C241T mutant stem loops with host transcription factor MADP1 indicating reduced replication efficiency. The results are also correlated with increased recovery rates and decreased death rates of global SARS-CoV-2 cases.

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    SciScore for 10.1101/2020.11.22.393009: (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
    Strains of various SARS CoV-2 already have reported a presence of various stem-loops structure and bulges which is addressed in RFAM database; we took FASTA format sequence (around 300 base pairs) from RFAM id RF03117 for studying 5’ UTR sequences of beta coronaviruses (
    RFAM
    suggested: (Rfam, RRID:SCR_007891)
    Salt concentration was set to 0.15 M sodium, and chloride ions to approximate physiological condition.
    Salt
    suggested: (SALT, RRID:SCR_003187)
    Plots and figures were generated in Pymol DeLano, W. L. 2009
    Pymol
    suggested: (PyMOL, RRID:SCR_000305)
    The DCCM analysis is carried out using the Bio3D packages of R (42) (43) (44) (45).
    Bio3D
    suggested: None

    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 27. 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 10.1101/2020.11.22.393009 on bioRxiv