Paired SARS-CoV-2 Spike Protein Mutations Observed During Ongoing SARS-CoV-2 Viral Transfer from Humans to Minks and Back to Humans

  1. Scott Burkholz
  2. Suman Pokhrel
  3. Benjamin R. Kraemer
  4. Daria Mochly-Rosen
  5. Richard T. Carback
  6. Tom Hodge
  7. Paul Harris
  8. Serban Ciotlos
  9. Lu Wang
  10. CV Herst
  11. Reid Rubsamen

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Abstract

A mutation analysis of SARS-CoV-2 genomes collected around the world sorted by sequence, date, geographic location, and species has revealed a large number of variants from the initial reference sequence in Wuhan. This analysis also reveals that humans infected with SARS-CoV-2 have infected mink populations in the Netherlands, Denmark, United States, and Canada. In these animals, a small set of mutations in the spike protein receptor binding domain (RBD), often occurring in specific combinations, has transferred back into humans. The viral genomic mutations in minks observed in the Netherlands and Denmark show the potential for new mutations on the SARS-CoV-2 spike protein RBD to be introduced into humans by zoonotic transfer. Our data suggests that close attention to viral transfer from humans to farm animals and pets will be required to prevent build-up of a viral reservoir for potential future zoonotic transfer.

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  1. ScreenIT

    SciScore for 10.1101/2020.12.22.424003: (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.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Mutation Discovery: All 235,299 available spike glycoprotein sequences available thru December 5th were downloaded from GISAID (Elbe & Buckland-Merrett
    Mutation Discovery
    suggested: None
    Spike glycoprotein sequences meeting those criteria were re-aligned via MAFFT (Katoh & Standley, 2013) against WIV04 (MN996528.1) (Zhou et al., 2020) with position numbering kept constant.
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    A custom Python (Python 3, 2020) script was utilized to compare the variants seen in mink and humans different from the WIV04 reference sequence.
    Python
    suggested: (IPython, RRID:SCR_001658)
    Residue positions were visualized in Jalview (Waterhouse et al., 2009).
    Jalview
    suggested: (Jalview, RRID:SCR_006459)
    Mutation Effect Calculations: Molecular Operating Environment (MOE)
    Mutation Effect Calculations
    suggested: (OMICtools, RRID:SCR_002250)
    The potential effect of variants was predicted using PROVEAN (Choi & Chan, 2015) with R (R. Core Team, 2017) and SIFT (Ng, 2003).
    PROVEAN
    suggested: (PROVEAN, RRID:SCR_002182)
    SIFT
    suggested: (SIFT, RRID:SCR_012813)

    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

    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 10.1101/2020.12.22.424003 on bioRxiv