Decoding the lethal effect of SARS-CoV-2 (novel coronavirus) strains from global perspective: molecular pathogenesis and evolutionary divergence

  1. Shuvam Banerjee
  2. Shrinjana Dhar
  3. Sandip Bhattacharjee
  4. Pritha Bhattacharjee

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Abstract

Background

COVID-19 is a disease with global public health emergency that have shook the world since its’ first detection in China in December, 2019. Severe acute respiratory syndrome Coronavirus 2 ( SARS-CoV-2 ) is the pathogen responsible behind this pandemic. The lethality of different viral strains is found to vary in different geographical locations but the molecular mechanism is yet to be known.

Methods

Available data of whole genome sequencing of different viral strains published by different countries were retrieved and then analysed using Multiple Sequence Alignment and Pair-wise Sequence Alignment leading to Phylogenetic tree construction. Each location and the corresponding genetic variations were screened in depth. Then the variations are analysed at protein level giving special emphasis on Non Synonymous amino acid substitutions. The fatality rates in different countries were matched against the mutation number, rarity of the nucleotide alterations and functional impact of the Non Synonymous changes at protein level, separately and in combination.

Findings

All the viral strains have been found to evolve from the viral strain of Taiwan (MT192759) which is 100% identical with the ancestor SARS-CoV-2 sequences of Wuhan (NC 045512.2; submitted on 5 th Jan, 2020). Transition from C to T (C>T) is the most frequent mutation in this viral genome and mutations A>T, G>A, T>A are the rarest ones, found in countries with maximum fatality rate i.e Italy, Spain and Sweden. 20 Non Synonymous mutations are located in viral genome spanning Orf1ab polyprotein, Surface glycoprotein, Nucleocapsid protein etc. The functional effect on the structure and function of the protein can favourably or unfavourably interact with the host body.

Interpretation

The fatality outcome depends on three important factors (a) number of mutation (b) rarity of the allelic variation and (c) functional consequence of the mutation at protein level. The molecular divergence, evolved from the ancestral strain (S) lead to extremely lethal (E), lethal(L) and non lethal (N) strains with the involvement of an Intermediate strain(I).

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    SciScore for 10.1101/2020.04.06.027854: (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
    Whole genomic data retrieval from the database: Retrieved the whole genome sequences from “NCBI Virus” database, specific input was “SARS-CoV-2”, during a period from Jan 5 through March 24, 2020.
    Virus”
    suggested: None
    Multiple Sequence Alignment and Evolutionary Dynamics: ClustalW (version 2.1) was employed to align multiple sequences, representative of 13 countries, with the purpose (a) to understand the similarity and variation in all genomic position, (b) to establish the evolutionary relationship among the viral strains affecting the whole world and (c) finally, to distinguish the ancestry of different viral strains using FastTree tool, which is based on Neighbour joining method.
    ClustalW
    suggested: (ClustalW, RRID:SCR_017277)
    FastTree
    suggested: (FastTree, RRID:SCR_015501)
    Our protein sequences were aligned with existing protein sequences of SARS-CoV-2 present in the ‘NCBI Virus’ database to check which ORF corresponds to the which known protein.
    Virus’
    suggested: None
    The functional impacts of all NS mutations at protein were analysed using different SNP annotation tools (i.e. SIFT, SNAP, Polyphen2 and MetaSNP).
    SIFT
    suggested: (SIFT, RRID:SCR_012813)
    SNAP
    suggested: (SNAP, RRID:SCR_007936)
    Polyphen2
    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: 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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  2. Version published to 10.1101/2020.04.06.027854v1 on bioRxiv