Spike residue 403 affects binding of coronavirus spikes to human ACE2
Copyright policy )Spike residue 403 affects binding of coronavirus spikes to human ACE2
AbstractThe 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.
- Karlsruhe Institute of Technology Germany
- Institute of Medical Microbiology and Hygiene Germany
- German Primate Center Germany
- University of Ulm Germany
- Karlsruhe Institute of Technology / KIT Germany
570, Technology, Molekularbiologie, ddc:600, COVID-19 Vaccines, Coronaviridae, Molecular biology, Science, 610, Coronaviren, Molecular Dynamics Simulation, Microbiology, Article, DDC 570 / Life sciences, Species Specificity, Zoonoses, DDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit, Animals, Humans, Cloning, Molecular, info:eu-repo/classification/ddc/610, info:eu-repo/classification/ddc/570, SARS-CoV-2, Stem Cells, Q, COVID-19, 600, HEK293 Cells, FOS: Biological sciences, Mutation, Spike Glycoprotein, Coronavirus, Mikrobiologie, info:eu-repo/classification/ddc/600, Replicon, Angiotensin-Converting Enzyme 2, Caco-2 Cells, DDC 610 / Medicine & health, Protein Binding
570, Technology, Molekularbiologie, ddc:600, COVID-19 Vaccines, Coronaviridae, Molecular biology, Science, 610, Coronaviren, Molecular Dynamics Simulation, Microbiology, Article, DDC 570 / Life sciences, Species Specificity, Zoonoses, DDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit, Animals, Humans, Cloning, Molecular, info:eu-repo/classification/ddc/610, info:eu-repo/classification/ddc/570, SARS-CoV-2, Stem Cells, Q, COVID-19, 600, HEK293 Cells, FOS: Biological sciences, Mutation, Spike Glycoprotein, Coronavirus, Mikrobiologie, info:eu-repo/classification/ddc/600, Replicon, Angiotensin-Converting Enzyme 2, Caco-2 Cells, DDC 610 / Medicine & health, Protein Binding
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