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, Bozzo CP, Volcic M, Koepke L, Mueller JA, Krueger J, Heller S, Stenger S, Hoffmann M, Poehlmann S, Kleger A, Jacob T, Conzelmann KK, Enßer A, Sparrer KMJ, Kirchhoff F (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 12

Article Number: 6855

Journal Issue: 1

DOI: 10.1038/s41467-021-27180-0

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.

Authors with CRIS profile

Alexandra Herrmann Institute of Clinical and Molecular Virology Arne Cordsmeier Institute of Clinical and Molecular Virology Armin Enßer Medizinische Fakultät

Involved external institutions

Universität Ulm DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Deutsches Primatenzentrum (DPZ), Leibniz-Institut für Primatenforschung DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE)

How to cite

APA:

Zech, F., Schniertshauer, D., Jung, C., Herrmann, A., Cordsmeier, A., Xie, Q.,... Kirchhoff, F. (2021). Spike residue 403 affects binding of coronavirus spikes to human ACE2. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-27180-0

MLA:

Zech, Fabian, et al. "Spike residue 403 affects binding of coronavirus spikes to human ACE2." Nature Communications 12.1 (2021).

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