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Molecular definition of SARS-CoV-2 RBD mutations: receptor affinity versus neutralization of receptor interaction
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  • Monique Vogel,
  • Gilles Augusto,
  • Xinyue Chang,
  • Xuelan Liu,
  • Daniel Speiser,
  • Mona Mohsen,
  • Martin Bachmann
Monique Vogel
Inselspital University Hospital Berne Institute of Immunology
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Gilles Augusto
University of Bern
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Xinyue Chang
University of Bern
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Xuelan Liu
Inselspital University Hospital Bern
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Daniel Speiser
Inselspital University Hospital Bern
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Mona Mohsen
University of Bern
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Martin Bachmann
Inselspital University Hospital Bern
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Abstract

Background: Several new variants of SARS-CoV-2 have emerged since fall 2020 which have multiple mutations in the receptor binding domain (RBD) of the spike protein. It is unclear which mutations affect receptor affinity versus immune recognition. Methods: We produced RBD with single mutations (E484K, K417N or N501Y) or with all three mutations combined and tested their binding to ACE2 by biolayer interferometry (BLI). The ability of convalescent sera to recognize RBDs and block their interaction with ACE2 was tested as well. Results: We demonstrated that single mutation N501Y increased binding affinity to ACE2 but did not significantly affect its recognition by convalescent sera. In contrast, single mutation E484K had almost no impact on the binding kinetics, but essentially abolished recognition of RBD by convalescent sera. Interestingly, combining mutations E484K, K417N and N501Y resulted in a RBD with both features: enhanced receptor binding and abolished immune recognition. Conclusion: Our data demonstrate that single mutations either affect receptor affinity or immune recognition while triple mutant RBDs combine both features.

Peer review status:ACCEPTED

19 Apr 2021Submitted to Allergy
20 Apr 2021Submission Checks Completed
20 Apr 2021Assigned to Editor
21 Apr 2021Reviewer(s) Assigned
04 May 2021Review(s) Completed, Editorial Evaluation Pending
04 May 2021Editorial Decision: Revise Minor
21 May 20211st Revision Received
22 May 2021Submission Checks Completed
22 May 2021Assigned to Editor
29 May 2021Reviewer(s) Assigned
31 May 2021Review(s) Completed, Editorial Evaluation Pending
03 Jun 2021Editorial Decision: Accept