SARS-CoV-2 Spike Mutations, L452R, T478K, E484Q and P681R, in the Second Wave of COVID-19 in Maharashtra, India

  1. Sarah Cherian
  2. Varsha Potdar
  3. Santosh Jadhav
  4. Pragya Yadav
  5. Nivedita Gupta
  6. Mousumi Das
  7. Partha Rakshit
  8. Sujeet Singh
  9. Priya Abraham
  10. Samiran Panda
  11. NIC Team

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Abstract

As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being used to investigate its transmission and evolution. Against the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches were undertaken to identify possible new variants and gauge the fitness of the current circulating strains. Phylogenetic analysis revealed that newly identified lineages B.1.617.1 and B.1.617.2 were predominantly circulating. The signature mutations possessed by these strains were L452R, T478K, E484Q, D614G and P681R in the spike protein, including within the receptor-binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R, T478K and E484Q revealed that these may possibly result in increased ACE2 binding while P681R in the furin cleavage site could increase the rate of S1-S2 cleavage, resulting in better transmissibility. The two RBD mutations, L452R and E484Q, indicated decreased binding to select monoclonal antibodies (mAbs) and may affect their neutralization potential. Further in vitro/in vivo studies would help confirm the phenotypic changes of the mutant strains. Overall, the study revealed that the newly emerged variants were responsible for the second wave of COVID-19 in Maharashtra. Lineage B.1.617.2 has been designated as a VOC delta and B.1.617.1 as a variant of interest kappa, and they are being widely reported in the rest of the country as well as globally. Continuous monitoring of these and emerging variants in India is essential.

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  1. Version published to 10.3390/microorganisms9071542
  2. Version published to 10.1101/2021.04.22.440932v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.04.22.440932: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The598 genomes werealigned using MUSCLE and aMaximum Likelihood phylogenetic tree was constructed using IQ-tree v1.611,12, employing the GTR as the substitution model and 1,000 bootstrap replications.
    MUSCLE
    suggested: (MUSCLE, RRID:SCR_011812)
    IQ-tree
    suggested: (IQ-TREE, RRID:SCR_017254)

    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.

    About SciScore

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  4. Version published to 10.1101/2021.04.22.440932v1 on bioRxiv