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Spike residue 403 affects binding of coronavirus spikes to human ACE2

Author

Listed:
  • Fabian Zech

    (Institute of Molecular Virology, Ulm University Medical Center)

  • Daniel Schniertshauer

    (Institute of Molecular Virology, Ulm University Medical Center)

  • Christoph Jung

    (Institute of Electrochemistry, Ulm University
    Helmholtz-Institute Ulm (HIU) Electrochemical Energy Storage, Helmholtz-Straße 16
    Karlsruhe Institute of Technology (KIT), P.O. Box 3640)

  • Alexandra Herrmann

    (Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg)

  • Arne Cordsmeier

    (Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg)

  • Qinya Xie

    (Institute of Molecular Virology, Ulm University Medical Center)

  • Rayhane Nchioua

    (Institute of Molecular Virology, Ulm University Medical Center)

  • Caterina Prelli Bozzo

    (Institute of Molecular Virology, Ulm University Medical Center)

  • Meta Volcic

    (Institute of Molecular Virology, Ulm University Medical Center)

  • Lennart Koepke

    (Institute of Molecular Virology, Ulm University Medical Center)

  • Janis A. Müller

    (Institute of Molecular Virology, Ulm University Medical Center)

  • Jana Krüger

    (Ulm University Medical Center)

  • Sandra Heller

    (Ulm University Medical Center)

  • Steffen Stenger

    (Institute of Medical Microbiology and Hygiene, Ulm University Medical Centre)

  • Markus Hoffmann

    (Infection Biology Unit, German Primate Center—Leibniz Institute for Primate Research)

  • Stefan Pöhlmann

    (Infection Biology Unit, German Primate Center—Leibniz Institute for Primate Research)

  • Alexander Kleger

    (Ulm University Medical Center)

  • Timo Jacob

    (Institute of Electrochemistry, Ulm University
    Helmholtz-Institute Ulm (HIU) Electrochemical Energy Storage, Helmholtz-Straße 16
    Karlsruhe Institute of Technology (KIT), P.O. Box 3640)

  • Karl-Klaus Conzelmann

    (Max von Pettenkofer-Institute of Virology, Medical Faculty, and Gene Center, Ludwig-Maximilians-Universität München)

  • Armin Ensser

    (Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg)

  • Konstantin M. J. Sparrer

    (Institute of Molecular Virology, Ulm University Medical Center)

  • Frank Kirchhoff

    (Institute of Molecular Virology, Ulm University Medical Center)

Abstract

The bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, the cause of the COVID-19 pandemic. However, this bat virus was most likely unable to directly infect humans since its Spike (S) protein does not interact efficiently with the human ACE2 receptor. Here, we show that a single T403R mutation increases binding of RaTG13 S to human ACE2 and allows VSV pseudoparticle infection of human lung cells and intestinal organoids. Conversely, mutation of R403T in the SARS-CoV-2 S reduces pseudoparticle infection and viral replication. The T403R RaTG13 S is neutralized by sera from individuals vaccinated against COVID-19 indicating that vaccination might protect against future zoonoses. Our data suggest that a positively charged amino acid at position 403 in the S protein is critical for efficient utilization of human ACE2 by S proteins of bat coronaviruses. This finding could help to better predict the zoonotic potential of animal coronaviruses.

Suggested Citation

  • Fabian Zech & Daniel Schniertshauer & Christoph Jung & Alexandra Herrmann & Arne Cordsmeier & Qinya Xie & Rayhane Nchioua & Caterina Prelli Bozzo & Meta Volcic & Lennart Koepke & Janis A. Müller & Jan, 2021. "Spike residue 403 affects binding of coronavirus spikes to human ACE2," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27180-0
    DOI: 10.1038/s41467-021-27180-0
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    1. Jun-Yu Si & Yuan-Mei Chen & Ye-Hui Sun & Meng-Xue Gu & Mei-Ling Huang & Lu-Lu Shi & Xiao Yu & Xiao Yang & Qing Xiong & Cheng-Bao Ma & Peng Liu & Zheng-Li Shi & Huan Yan, 2024. "Sarbecovirus RBD indels and specific residues dictating multi-species ACE2 adaptiveness," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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