TY - JOUR T1 - Spike mutation T403R allows bat coronavirus RaTG13 to use human ACE2 JF - bioRxiv DO - 10.1101/2021.05.31.446386 SP - 2021.05.31.446386 AU - Fabian Zech AU - Daniel Schniertshauer AU - Christoph Jung AU - Alexandra Herrmann AU - Qinya Xie AU - Rayhane Nchioua AU - Caterina Prelli Bozzo AU - Meta Volcic AU - Lennart Koepke AU - Jana Krüger AU - Sandra Heller AU - Alexander Kleger AU - Timo Jacob AU - Karl-Klaus Conzelmann AU - Armin Ensser AU - Konstantin M.J. Sparrer AU - Frank Kirchhoff Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/31/2021.05.31.446386.abstract N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the COVID-19 pandemic, most likely emerged from bats1. A prerequisite for this devastating zoonosis was the ability of the SARS-CoV-2 Spike (S) glycoprotein to use human angiotensin-converting enzyme 2 (ACE2) for viral entry. Although the S protein of the closest related bat virus, RaTG13, shows high similarity to the SARS-CoV-2 S protein it does not efficiently interact with the human ACE2 receptor2. Here, we show that a single T403R mutation allows the RaTG13 S to utilize the human ACE2 receptor for infection of human cells and intestinal organoids. Conversely, mutation of R403T in the SARS-CoV-2 S significantly reduced ACE2-mediated virus infection. The S protein of SARS-CoV-1 that also uses human ACE2 also contains a positive residue (K) at this position, while the S proteins of CoVs utilizing other receptors vary at this location. Our results indicate that the presence of a positively charged amino acid at position 403 in the S protein is critical for efficient utilization of human ACE2. This finding could help to predict the zoonotic potential of animal coronaviruses.Competing Interest StatementThe authors have declared no competing interest. ER -