An ACE2-dependent Sarbecovirus in Russian bats is resistant to SARS-CoV-2 vaccines

  1. Stephanie N. Seifert
  2. Shuangyi Bai
  3. Stephen Fawcett
  4. Elizabeth B. Norton
  5. Kevin J. Zwezdaryk
  6. James Robinson
  7. Bronwyn Gunn
  8. Michael Letko

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Spillover of sarbecoviruses from animals to humans has resulted in outbreaks of severe acute respiratory syndrome SARS-CoVs and the ongoing COVID-19 pandemic. Efforts to identify the origins of SARS-CoV-1 and -2 has resulted in the discovery of numerous animal sarbecoviruses–the majority of which are only distantly related to known human pathogens and do not infect human cells. The receptor binding domain (RBD) on sarbecoviruses engages receptor molecules on the host cell and mediates cell invasion. Here, we tested the receptor tropism and serological cross reactivity for RBDs from two sarbecoviruses found in Russian horseshoe bats. While these two viruses are in a viral lineage distinct from SARS-CoV-1 and -2, the RBD from one virus, Khosta 2, was capable of using human ACE2 to facilitate cell entry. Viral pseudotypes with a recombinant, SARS-CoV-2 spike encoding for the Khosta 2 RBD were resistant to both SARS-CoV-2 monoclonal antibodies and serum from individuals vaccinated for SARS-CoV-2. Our findings further demonstrate that sarbecoviruses circulating in wildlife outside of Asia also pose a threat to global health and ongoing vaccine campaigns against SARS-CoV-2

Article activity feed

  1. Version published to 10.1371/journal.ppat.1010828
  2. Version published to 10.1101/2021.12.05.471310v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.12.05.471310: (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.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Cells and pseudotype assay: 293T, Huh-7 (human liver cells), and BHKs were maintained under standard cell culture conditions in DMEM with L-glutamine, antibiotics, and 10
    Huh-7
    suggested: None
    Westernblot: Viral pseudotypes were concentrated and 293T producer cells were lysed in 1% SDS and clarified as described previously1.
    293T
    suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
    Recombinant DNA
    SentencesResources
    Spike sequences from HCoV-229E (AB691763.1), MERS-CoV (JX869059.2), and SARS-CoV-1 (AY278741) were codon-optimized, appended with a carboxy-terminal FLAG tag sequence separated by a flexible poly-glycine linker and cloned into pcDNA3.1+ as previously described1.
    pcDNA3.1+
    suggested: RRID:Addgene_117272)
    Software and Algorithms
    SentencesResources
    Amino acid sequences for the receptor binding domain of the spike glycoprotein were aligned using ClustalW multiple sequence alignment with default parameters.
    ClustalW
    suggested: (ClustalW, RRID:SCR_017277)
    A maximum likelihood phylogenetic tree was inferred with PhyML v.
    PhyML
    suggested: (PhyML, RRID:SCR_014629)
    The final tree was then visualized as a cladogram with FigTree v1.4.4 (https://github.com/rambaut/figtree).
    FigTree
    suggested: (FigTree, RRID:SCR_008515)

    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.

    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.

  4. Version published to 10.1101/2021.12.05.471310v1 on bioRxiv