| Title: |
Spike residue 403 affects binding of coronavirus spikes to human ACE2 |
| Authors: |
Zech, Fabian; Schniertshauer, Daniel; Jung, Christoph; Herrmann, Alexandra; Cordsmeier, Arne; Xie, Qinya; Nchioua, Rayhane; Prelli Bozzo, Caterina; Volčič, Meta; Koepke, Lennart; Müller, Janis A.; Krüger, Jana; Heller, Sandra; Stenger, Steffen; Hoffmann, Markus; Pöhlmann, Stefan; Kleger, Alexander; Jacob, Timo; Conzelmann, Karl-Klaus; Ensser, Armin; Sparrer, Konstantin M.J.; Kirchhoff, Frank |
| Publisher Information: |
Universität Ulm |
| Publication Year: |
2021 |
| Collection: |
OPARU (OPen Access Repository of Ulm University) |
| Subject Terms: |
Microbiology; Molecular biology; Coronaviridae; Mikrobiologie; Molekularbiologie; Coronaviren |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| DOI: |
10.18725/OPARU-42066 |
| Availability: |
https://doi.org/10.18725/OPARU-42066; http://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-42142-0 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.E0FEF598 |
| Database: |
BASE |