Pathogenetic Perspective of Missense Mutations of ORF3a Protein of SARS-CoV2

  1. Sk. Sarif Hassan
  2. Diksha Attrish
  3. Shinjini Ghosh
  4. Pabitra Pal Choudhury
  5. Bidyut Roy

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Abstract

One of the most important proteins for COVID-19 pathogenesis in SARS-CoV2 is the ORF3a protein which is the largest accessory protein among others accessory proteins coded by coronavirus genome. The major roles of the protein include virulence, infectivity, ion channel activity, morphogenesis and virus release. The coronavirus, SARS-CoV2 is continuously evolving naturally and thereby the encoded proteins are also mutating rapidly. Therefore, critical study of mutations in ORF3a is certainty important from the pathogenetic perspective. Here, a sum of 175 various non-synonymous mutations in the ORF3a protein of SARS-CoV2 are identified and their corresponding effects in structural stability and functions of the protein ORF3a are studied. Broadly three different classes of mutations, such as neutral, disease and mixed (neutral and disease) type mutations were observed. Consecutive mutations in some ORF3a proteins are established based on timeline of detection of mutations. Considering the amino acid compositions over the ORF3a primary protein sequences, twenty clusters are detected based on K-means clustering method. Our findings on 175 novel mutations of ORF3a proteins will extend our knowledge of ORF3a, a vital accessory protein in SARS-CoV2, which would assist to enlighten on the pathogenicity of this life-threatening COVID-19.

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    SciScore for 10.1101/2020.08.04.236653: (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
    Here we discuss about data followed by methods which are employed in this study. 2.1. Data: As on date 27th July, 2020, there were 7194 complete genomes of SARS-CoV2 available in the NCBI database and accordingly each genome contains one of the accessory proteins ORF3a and among them only 296 sequences are found to be distinct from each other.
    NCBI
    suggested: (NCBI, RRID:SCR_006472)
    In this study we did clustering using Matlab by customizing the value of K and inputting the frequency of amino acid compositions over the ORF3a proteins.
    Matlab
    suggested: (MATLAB, RRID:SCR_001622)

    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 10.1101/2020.08.04.236653 on bioRxiv