Spike mutation T403R allows bat coronavirus RaTG13 to use human ACE2
Zech, F.; Schniertshauer, D.; Jung, C.; Herrmann, A.; Xie, Q.; Nchioua, R.; Prelli Bozzo, C.; Volcic, M.; Koepke, L.; Krueger, J.; Heller, S.; Kleger, A.; Jacob, T.; Conzelmann, K.-K.; Ensser, A.; Sparrer, K. M. J.; Kirchhoff, F.
Show abstract
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.
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