Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants.

Autor:	Bayarri-Olmos R; Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Jarlhelt I; Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Johnsen LB; Recombinant Technologies, Novo Nordisk A/S, Måløv, Denmark., Hansen CB; Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Helgstrand C; Recombinant Technologies, Novo Nordisk A/S, Måløv, Denmark., Rose Bjelke J; Recombinant Technologies, Novo Nordisk A/S, Måløv, Denmark., Matthiesen F; Recombinant Technologies, Novo Nordisk A/S, Måløv, Denmark., Nielsen SD; Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Iversen KK; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Emergency Medicine, Herlev and Gentofte Hospital, Copenhagen, Denmark., Ostrowski SR; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; The Blood Bank, Department of Clinical Immunology, Section 2034, Rigshospitalet, Copenhagen, Denmark., Bundgaard H; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Cardiology, Rigshospitalet, Copenhagen, Denmark., Frikke-Schmidt R; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark., Garred P; Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Skjoedt MO; Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; Institute of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Oct 07; Vol. 12, pp. 757197. Date of Electronic Publication: 2021 Oct 07 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.757197
Abstrakt:	The recent identification and rise to dominance of the P.1 and B.1.351 SARS-CoV-2 variants have brought international concern because they may confer fitness advantages. The same three positions in the receptor-binding domain (RBD) are affected in both variants, but where the 417 substitution differs, the E484K/N501Y have co-evolved by convergent evolution. Here we characterize the functional and immune evasive consequences of the P.1 and B.1.351 RBD mutations. E484K and N501Y result in gain-of-function with two different outcomes: The N501Y confers a ten-fold affinity increase towards ACE-2, but a modest antibody evasion potential of plasma from convalescent or vaccinated individuals, whereas the E484K displays a significant antibody evasion capacity without a major impact on affinity. On the other hand, the two different 417 substitutions severely impair the RBD/ACE-2 affinity, but in the combined P.1 and B.1.351 RBD variants, this effect is partly counterbalanced by the effect of the E484K and N501Y. Our results suggest that the combination of these three mutations is a two-step forward and one step back in terms of viral fitness. Competing Interests: LBJ, CH, JRB and FM were employed by Novo Nordisk A/S. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Bayarri-Olmos, Jarlhelt, Johnsen, Hansen, Helgstrand, Rose Bjelke, Matthiesen, Nielsen, Iversen, Ostrowski, Bundgaard, Frikke-Schmidt, Garred and Skjoedt.)
Databáze:	MEDLINE
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