Spike residue 403 affects binding of coronavirus spikes to human ACE2

The bat sarbecovirus RaTG13, a close relative of SARS-CoV-2, likely couldn't directly infect humans due to its Spike (S) protein's inefficient interaction with human ACE2. A single T403R mutation in RaTG13 S increases its binding to human ACE2, enabling infection of human lung cells and intestinal organoids. Conversely, R403T mutation in SARS-CoV-2 S reduces infection. COVID-19 vaccine sera neutralize T403R RaTG13 S, suggesting vaccine protection against future zoonotic events. A positively charged amino acid at position 403 in the S protein is crucial for bat coronavirus S proteins to use human ACE2.

Fabian Zech, Daniel Schnierthauer, 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 Enserink, Konstantin M J Sparrer, Frank Kirchhoff