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Spike residue 403 affects binding of coronavirus spikes to human ACE2

Zech, F.; Schniertshauer, D.; Jung, C.; Herrmann, A.; Cordsmeier, A.; Xie, Q.; Nchioua, R.; Prelli Bozzo, C.; Volcic, M.; Koepke, L.; Müller, J. A.; Krüger, J.; Heller, S.; Stenger, S.; Hoffmann, M.; Pöhlmann, S.; Kleger, A.; Jacob, T.; Conzelmann, K.-K.; ... mehr


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.

Verlagsausgabe §
DOI: 10.5445/IR/1000140893
Veröffentlicht am 08.12.2021
DOI: 10.1038/s41467-021-27180-0
Zitationen: 11
Web of Science
Zitationen: 11
Zitationen: 16
Cover der Publikation
Zugehörige Institution(en) am KIT Helmholtz-Institut Ulm (HIU)
Publikationstyp Zeitschriftenaufsatz
Publikationsdatum 25.11.2021
Sprache Englisch
Identifikator ISSN: 2041-1723
KITopen-ID: 1000140893
HGF-Programm 38.02.02 (POF IV, LK 01) Components and Cells
Erschienen in Nature Communications
Verlag Nature Research
Band 12
Heft 1
Seiten 6855
Nachgewiesen in Scopus
Web of Science
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