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Spike residue 403 affects binding of coronavirus spikes to human ACE2.
Zech, Fabian; Schniertshauer, Daniel; Jung, Christoph; Herrmann, Alexandra; Cordsmeier, Arne; Xie, Qinya; Nchioua, Rayhane; Prelli Bozzo, Caterina; Volcic, Meta; Koepke, Lennart; Müller, Janis A; Krüger, Jana; Heller, Sandra; Stenger, Steffen; Hoffmann, Markus; Pöhlmann, Stefan; Kleger, Alexander; Jacob, Timo; Conzelmann, Karl-Klaus; Ensser, Armin; Sparrer, Konstantin M J; Kirchhoff, Frank.
  • Zech F; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Schniertshauer D; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Jung C; Institute of Electrochemistry, Ulm University, 89081, Ulm, Germany.
  • Herrmann A; Helmholtz-Institute Ulm (HIU) Electrochemical Energy Storage, Helmholtz-Straße 16, 89081, Ulm, Germany.
  • Cordsmeier A; Karlsruhe Institute of Technology (KIT), P.O. Box 3640, 76021, Karlsruhe, Germany.
  • Xie Q; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054, Erlangen, Germany.
  • Nchioua R; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054, Erlangen, Germany.
  • Prelli Bozzo C; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Volcic M; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Koepke L; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Müller JA; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Krüger J; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Heller S; Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
  • Stenger S; Department of Internal Medicine I, Ulm University Medical Center, 89081, Ulm, Germany.
  • Hoffmann M; Department of Internal Medicine I, Ulm University Medical Center, 89081, Ulm, Germany.
  • Pöhlmann S; Institute of Medical Microbiology and Hygiene, Ulm University Medical Centre, 89081, Ulm, Germany.
  • Kleger A; Infection Biology Unit, German Primate Center-Leibniz Institute for Primate Research, Göttingen, Germany.
  • Jacob T; Infection Biology Unit, German Primate Center-Leibniz Institute for Primate Research, Göttingen, Germany.
  • Conzelmann KK; Department of Internal Medicine I, Ulm University Medical Center, 89081, Ulm, Germany.
  • Ensser A; Institute of Electrochemistry, Ulm University, 89081, Ulm, Germany.
  • Sparrer KMJ; Helmholtz-Institute Ulm (HIU) Electrochemical Energy Storage, Helmholtz-Straße 16, 89081, Ulm, Germany.
  • Kirchhoff F; Karlsruhe Institute of Technology (KIT), P.O. Box 3640, 76021, Karlsruhe, Germany.
Nat Commun ; 12(1): 6855, 2021 11 25.
Article in English | MEDLINE | ID: covidwho-1537312
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Binding / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Type of study: Prognostic study Topics: Vaccines Limits: Animals / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-27180-0

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Binding / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Type of study: Prognostic study Topics: Vaccines Limits: Animals / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-27180-0