Local emergence and decline of a SARS-CoV-2 variant with mutations L452R and N501Y in the spike protein

  1. Jan-Philipp Mallm
  2. Christian Bundschuh
  3. Heeyoung Kim
  4. Niklas Weidner
  5. Simon Steiger
  6. Isabelle Lander
  7. Kathleen Börner
  8. Katharina Bauer
  9. Daniel Hübschmann
  10. Vladimir Benes
  11. Tobias Rausch
  12. Nayara Trevisan Doimo de Azevedo
  13. Anja Telzerow
  14. Katharina Laurence Jost
  15. Sylvia Parthé
  16. Paul Schnitzler
  17. Michael Boutros
  18. Barbara Müller
  19. Ralf Bartenschlager
  20. Hans-Georg Kräusslich
  21. Karsten Rippe

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Abstract

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are replacing the initial wild-type strain, jeopardizing current efforts to contain the pandemic. Amino acid exchanges in the spike protein are of particular concern as they can render the virus more transmissible or reduce vaccine efficacy. Here, we conducted whole genome sequencing of SARS-CoV-2 positive samples from the Rhine-Neckar district in Germany during January-March 2021. We detected a total of 166 samples positive for a variant with a distinct mutational pattern in the spike gene comprising L18F, L452R, N501Y, A653V, H655Y, D796Y and G1219V with a later gain of A222V. This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains. These observations strongly argue for continuous and comprehensive monitoring of SARS-CoV-2 evolution on a population level.

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    SciScore for 10.1101/2021.04.27.21254849: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethical statement: This study was approved by the ethics committee of the Medical Faculty at the University of Heidelberg for the analysis of proband samples by whole genome sequencing of the viral RNA (S-316/2021) as well as the virus propagation and neutralization assays and use of sera from vaccinated donors (S-203/2021).
    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
    Supernatant was collected (passage 0), centrifuged at 1,200 x g for 5 min and 0.35ml were used to inoculate 3×106 Vero E6 cells, seeded into a T25 cm2 flask one day prior to inoculation, in a total volume of 5 ml complete DMEM.
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Variant calling employed FreeBayes (37) and bcftools (38) for quality-filtering and normalization of variants.
    FreeBayes
    suggested: (FreeBayes, RRID:SCR_010761)
    Samtools, bcftools and iVar were also employed for viral consensus sequence generation.
    Samtools
    suggested: (SAMTOOLS, RRID:SCR_002105)
    Dose response curves were generated by non-linear regression sigmoidal dose response analysis with Prism 7 (GraphPad Software).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Data availability: SARS-CoV-2
    SARS-CoV-2
    suggested: (BioLegend Cat# 944703, RRID:AB_2890874)

    Results from OddPub: Thank you for sharing your data.

    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.

  2. Version published to 10.1101/2021.04.27.21254849v1 on medRxiv