Omicron (BA.1) and sub‐variants (BA.1.1, BA.2, and BA.3) of SARS‐CoV‐2 spike infectivity and pathogenicity: A comparative sequence and structural‐based computational assessment

  1. Suresh Kumar
  2. Kalimuthu Karuppanan
  3. Gunasekaran Subramaniam

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Abstract

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has now spread throughout the world. We used computational tools to assess the spike infectivity, transmission, and pathogenicity of Omicron (BA.1) and sub‐variants (BA.1.1, BA.2, and BA.3) in this study. BA.1 has 39 mutations, BA.1.1 has 40 mutations, BA.2 has 31 mutations, and BA.3 has 34 mutations, with 21 shared mutations between all. We observed 11 common mutations in Omicron's receptor‐binding domain (RBD) and sub‐variants. In pathogenicity analysis, the Y505H, N786K, T95I, N211I, N856K, and V213R mutations in omicron and sub‐variants are predicted to be deleterious. Due to the major effect of the mutations characterizing in the RBD, we found that Omicron and sub‐variants had a higher positive electrostatic surface potential. This could increase interaction between RBD and negative electrostatic surface potential human angiotensin‐converting enzyme 2 (hACE2). Omicron and sub‐variants had a higher affinity for hACE2 and the potential for increased transmission when compared to the wild‐type (WT). Negative electrostatic potential of N‐terminal domain (NTD) of the spike protein value indicates that the Omicron variant binds receptors less efficiently than the WT. Given that at least one receptor is highly expressed in lung and bronchial cells, the electrostatic potential of NTD negative value could be one of the factors contributing to why the Omicron variant is thought to be less harmful to the lower respiratory tract. Among Omicron sub‐lineages, BA.2 and BA.3 have a higher transmission potential than BA.1 and BA.1.1. We predicted that mutated residues in BA.1.1 (K478), BA.2 (R400, R490, and R495), and BA.3 (R397 and H499) formation of new salt bridges and hydrogen bonds. Omicron and sub‐variant mutations at Receptor‐binding Motif (RBM) residues such as Q493R, N501Y, Q498, T478K, and Y505H all contribute significantly to binding affinity with human ACE2. Interactions with Omicron variant mutations at residues 493, 496, 498, and 501 seem to restore ACE2 binding effectiveness lost due to other mutations like K417N.

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  1. Version published to 10.1002/jmv.27927
  2. ScreenIT

    SciScore for 10.1101/2022.02.11.480029: (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

    Experimental Models: Organisms/Strains
    SentencesResources
    2.3 Physiochemical characterization: Using the Expasy protparam 14, the protein sequences of BA.1, BA.1.1, BA.2, and BA.3’s whole spike protein and RBD were compared to Wuhan-Hu-1 (Wild type).
    Wuhan-Hu-1
    suggested: None
    Software and Algorithms
    SentencesResources
    2.2 Multiple alignment of Omicron Variants with Wild Type: Using Clustal Omega 13 with the default settings, the protein sequence of Wuhan-Hu-1 (Wild type) was aligned with the protein sequences of omicron variant and sub-lineages BA.1, BA.1.1, BA.2, and BA.3.
    Clustal Omega
    suggested: (Clustal Omega, RRID:SCR_001591)
    The Receptor-binding domain of Omicron and sub-variants were computed for electrostatic potential using electrostatic potential calculated with the Adaptive Poisson–Boltzmann Solver (APBS) program implemented in PyMOL 21.
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)
    2.7 Pathogenicity analysis: PredictSNP 24 was used to determine the pathogenicity of all mutations.
    PredictSNP
    suggested: (PredictSNP, RRID:SCR_006327)
    Using the PredictSNP web server, prediction algorithms from programmes like as MAPP, PolyPhen1 and PolyPhen-2, SIFT, SNAP, and PANTHER were utilised to achieve a consensus pathogenicity score.
    MAPP
    suggested: (MAPP, RRID:SCR_010775)
    PolyPhen1
    suggested: None
    PolyPhen-2
    suggested: None
    SIFT
    suggested: (SIFT, RRID:SCR_012813)
    SNAP
    suggested: (SNAP, RRID:SCR_007936)
    PANTHER
    suggested: (PANTHER, RRID:SCR_004869)

    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.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2022.02.11.480029 on bioRxiv