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Spike residue 403 affects binding of coronavirus spikes to human ACE2

Nat Commun. 2021-11; 
Fabian Zech, Daniel Schniertshauer, Christoph Jung, Alexandra Herrmann, Arne Cordsmeier, Qinya Xie, Rayhane Nchioua, Caterina Prelli Bozzo, Meta Volcic, Lennart Koepke, Janis A Müller, Jana Krüger, Sandra Heller, Steffen Stenger, Markus Hoffmann, Stefan Pöhlmann, Alexander Kleger, Timo Jacob, Karl-Klaus Conzelmann, Armin Ensser, Konstantin M J Sparrer, Frank Kirchhoff
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摘要

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 pos... More

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