The Rise and Fall of a Local SARS-CoV-2 Variant with the Spike Protein Mutation L452R

  1. Orna Mor
  2. Michal Mandelboim
  3. Shay Fleishon
  4. Efrat Bucris
  5. Dana Bar-Ilan
  6. Michal Linial
  7. Ital Nemet
  8. Limor Kliker
  9. Yaniv Lustig
  10. Israel National Consortium for SARS-CoV-2 Sequencing
  11. Ella S. Mendelson
  12. Neta S. Zuckerman

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Abstract

Emerging SARS-CoV-2 variants may threaten global vaccination efforts and the awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants among efforts undertaken to prevent further disease spread.

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  1. Version published to 10.3390/vaccines9080937
  2. ScreenIT

    SciScore for 10.1101/2021.07.03.21259957: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Sample collection for sequencing: Random sampling and systematic collection of PCR-positive samples for SARS-CoV-2 whole genome sequencing (WGS) was initiated in December 2020 and is now routinely conducted in Israel as part of a national effort for monitoring SARS-CoV-2 variants.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Virus-serum mixtures were added to the VERO-E6 cells and incubated for five days at 33°C, after which Gentain violet staining (1%) was used to stain and fix the cell culture layer.
    VERO-E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Sample collection for sequencing: Random sampling and systematic collection of PCR-positive samples for SARS-CoV-2 whole genome sequencing (WGS) was initiated in December 2020 and is now routinely conducted in Israel as part of a national effort for monitoring SARS-CoV-2 variants.
    WGS
    suggested: None
    Bioinformatics analysis: Fastq files were subjected to quality control using FastQC (www.bioinformatics.babraham.ac.uk/projects/fastqc/) and MultiQC [19] and low-quality sequences were filtered using trimmomatic [20].
    FastQC
    suggested: (FastQC, RRID:SCR_014583)
    MultiQC
    suggested: (MultiQC, RRID:SCR_014982)
    trimmomatic
    suggested: (Trimmomatic, RRID:SCR_011848)
    Sequences were mapped to the SARS-CoV-2 reference genomes (NC_045512.2) using Burrows-Wheeler aligner (BWA) mem [21]
    BWA
    suggested: (BWA, RRID:SCR_010910)
    Resulting BAM files were sorted, indexed and subjected to quality control using SAMtools suite [22].
    SAMtools
    suggested: (SAMTOOLS, RRID:SCR_002105)
    Multiple alignment of sample sequences with SARS-CoV-2 reference genome (NC_045512.2) was done using MAFFT [23].
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    Mutation calling, translation to amino acid and identification of P681H variant sequences were done in R with a custom code using Bioconductor package Seqinr [24].
    Bioconductor
    suggested: (Bioconductor, RRID:SCR_006442)
    Phylogenetic trees were constructed using the Augur pipeline [26].
    Augur
    suggested: None
    Sequences were aligned to SARS-CoV-2 reference genome (NC_045512.2) using MAFFT [23], and a time-resolved phylogenetic tree was constructed with IQ-Tree [27] and TreeTime [28] under the generalized time reversible (GTR) substitution model and visualized with auspice [26].
    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.
    • 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.

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

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.07.03.21259957v1 on medRxiv