Spike residue 403 affects binding of coronavirus spikes to human ACE2
peer-reviewed
Erstveröffentlichung
2021-11-25Authors
Zech, Fabian
Schniertshauer, Daniel
Jung, Christoph
Herrmann, Alexandra
Cordsmeier, Arne
Wissenschaftlicher Artikel
Published in
Nature Communications ; 12 (2021). - Art.-Nr. 6855. - eISSN 2041-1723
Link to original publication
https://dx.doi.org/10.1038/s41467-021-27180-0Faculties
Fakultät für NaturwissenschaftenInstitutions
UKU. Institut für Molekulare VirologieInstitut für Elektrochemie
UKU. Klinik für Innere Medizin I
UKU. Institut für Medizinische Mikrobiologie und Hygiene
External cooperations
Karlsruher Institut für TechnologieUniversitätsklinikum Erlangen
Helmholtz-Institut Ulm
Deutsche Primatenzentrum GmbH, Leibniz-Institut für Primatenforschung
Ludwig-Maximilians-Universität München
Document version
published version (publisher's PDF)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.
DFG Project THU
SFB 1279 / Nutzung des menschlichen Peptidoms für die Entwicklung neuer antimikrobieller und anti-Krebs Therapeutika / DFG / 316249678
SPP 1923 / Innate Sensing and Restriction of Retroviruses / DFG / 273898015
Charakterisierung der Manipulation der angeborenen Immunabwehr durch ORF3a, ORF6 und ORF7a von SARS-CoV-2 / DFG / 458681942 [SP 1600/6-1]
SPP 1923 / Innate Sensing and Restriction of Retroviruses / DFG / 273898015
Charakterisierung der Manipulation der angeborenen Immunabwehr durch ORF3a, ORF6 und ORF7a von SARS-CoV-2 / DFG / 458681942 [SP 1600/6-1]
Project uulm
IMMUNOMOD - Erforschung von neuartigen Strategien zur Unterstützung des angeborenen Immunsystems, um virale Erkrankungen zu bekämpfen / BMBF / 01KI2014
Publication funding
Open-Access-Förderung durch die Medizinische Fakultät der Universität Ulm
Is supplemented by
https://www.nature.com/articles/s41467-021-27180-0#Sec33https://www.nature.com/articles/s41467-021-27180-0#Sec34
Subject headings
[GND]: Mikrobiologie | Molekularbiologie | Coronaviren[MeSH]: Molecular biology | Microbiology | Coronaviridae
[Free subject headings]: Microbiology | Molecular biology
[DDC subject group]: DDC 570 / Life sciences | DDC 610 / Medicine & health
Metadata
Show full item recordDOI & citation
Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-42066
Zech, Fabian et al. (2022): Spike residue 403 affects binding of coronavirus spikes to human ACE2. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-42066
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