Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants

  1. Meng Yuan
  2. Deli Huang
  3. Chang-Chun D. Lee
  4. Nicholas C. Wu
  5. Abigail M. Jackson
  6. Xueyong Zhu
  7. Hejun Liu
  8. Linghang Peng
  9. Marit J. van Gils
  10. Rogier W. Sanders
  11. Dennis R. Burton
  12. S. Momsen Reincke
  13. Harald Prüss
  14. Jakob Kreye
  15. David Nemazee
  16. Andrew B. Ward
  17. Ian A. Wilson

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Abstract

Our key defense against the COVID-19 pandemic is neutralizing antibodies against the SARS-CoV-2 virus elicited by natural infection or vaccination. Recent emerging viral variants have raised concern because of their potential to escape antibody neutralization. Wang et al . identified four antibodies from early-outbreak convalescent donors that are potent against 23 variants, including variants of concern, and characterized their binding to the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yuan et al . examined the impact of emerging mutations in the receptor-binding domain of the spike protein on binding to the host receptor ACE2 and to a range of antibodies. These studies may be helpful for developing more broadly effective vaccines and therapeutic antibodies. —VV

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  1. Version published to 10.1126/science.abh1139
  2. ScreenIT

    SciScore for 10.1101/2021.02.16.430500: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Pseudovirions were generated by co-transfection of HEK293T cells with plasmids encoding MLV-gag/pol, MLV-CMV-Luciferase, and SARS-CoV-2 spike WT (GenBank: MN908947) or variants with an 18-AA truncation at the C-terminus.
    HEK293T
    suggested: None
    After incubation, 10,000 Hela-hACE2 cells, generated by lentivirus transduction of wild-type Hela cells and enriched by fluorescence-activated cell sorting (FACS) using biotinylated SARS-CoV-2 RBD conjugated with streptavidin-Alexa Fluor 647 (Thermo, S32357), were added to the mixture with 20 µg/ml Dextran (Sigma, 93556-1G) to enhance infectivity.
    Hela-hACE2
    suggested: None
    Hela
    suggested: None
    The S plasmid was transfected into HEK293F cells and the supernatant was harvested 6 days post-transfection.
    HEK293F
    suggested: RRID:CVCL_6642)
    Software and Algorithms
    SentencesResources
    Iterative model building and refinement were carried out in COOT (6) and PHENIX (7), respectively.
    COOT
    suggested: (Coot, RRID:SCR_014222)
    PHENIX
    suggested: (Phenix, RRID:SCR_014224)
    Neutralization ID50 titers or IC50 values were calculated using “One-Site Fit LogIC50” regression in GraphPad Prism 9.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.

    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 10.1101/2021.02.16.430500v1 on bioRxiv