tetano
Editor, Senior Moderator
Nat Commun
. 2021 Nov 25;12(1):6855.
doi: 10.1038/s41467-021-27180-0.
Spike residue 403 affects binding of coronavirus spikes to human ACE2
Fabian Zech[SUP] 1 [/SUP], Daniel Schniertshauer[SUP] 1 [/SUP], Christoph Jung[SUP] 2 3 4 [/SUP], Alexandra Herrmann[SUP] 5 [/SUP], Arne Cordsmeier[SUP] 5 [/SUP], Qinya Xie[SUP] 1 [/SUP], Rayhane Nchioua[SUP] 1 [/SUP], Caterina Prelli Bozzo[SUP] 1 [/SUP], Meta Volcic[SUP] 1 [/SUP], Lennart Koepke[SUP] 1 [/SUP], Janis A Müller[SUP] 1 [/SUP], Jana Krüger[SUP] 6 [/SUP], Sandra Heller[SUP] 6 [/SUP], Steffen Stenger[SUP] 7 [/SUP], Markus Hoffmann[SUP] 8 [/SUP], Stefan Pöhlmann[SUP] 8 [/SUP], Alexander Kleger[SUP] 6 [/SUP], Timo Jacob[SUP] 2 3 4 [/SUP], Karl-Klaus Conzelmann[SUP] 9 [/SUP], Armin Ensser[SUP] 5 [/SUP], Konstantin M J Sparrer[SUP] 1 [/SUP], Frank Kirchhoff[SUP] 10 [/SUP]
Affiliations
Abstract
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.
. 2021 Nov 25;12(1):6855.
doi: 10.1038/s41467-021-27180-0.
Spike residue 403 affects binding of coronavirus spikes to human ACE2
Fabian Zech[SUP] 1 [/SUP], Daniel Schniertshauer[SUP] 1 [/SUP], Christoph Jung[SUP] 2 3 4 [/SUP], Alexandra Herrmann[SUP] 5 [/SUP], Arne Cordsmeier[SUP] 5 [/SUP], Qinya Xie[SUP] 1 [/SUP], Rayhane Nchioua[SUP] 1 [/SUP], Caterina Prelli Bozzo[SUP] 1 [/SUP], Meta Volcic[SUP] 1 [/SUP], Lennart Koepke[SUP] 1 [/SUP], Janis A Müller[SUP] 1 [/SUP], Jana Krüger[SUP] 6 [/SUP], Sandra Heller[SUP] 6 [/SUP], Steffen Stenger[SUP] 7 [/SUP], Markus Hoffmann[SUP] 8 [/SUP], Stefan Pöhlmann[SUP] 8 [/SUP], Alexander Kleger[SUP] 6 [/SUP], Timo Jacob[SUP] 2 3 4 [/SUP], Karl-Klaus Conzelmann[SUP] 9 [/SUP], Armin Ensser[SUP] 5 [/SUP], Konstantin M J Sparrer[SUP] 1 [/SUP], Frank Kirchhoff[SUP] 10 [/SUP]
Affiliations
- PMID: 34824253
- DOI: 10.1038/s41467-021-27180-0
Abstract
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.