Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{b6211b9f924f48be888e1fa49057556f,
title = "Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants",
abstract = "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.",
author = "Rafael Bayarri-Olmos and Ida Jarlhelt and Johnsen, {Laust Bruun} and Hansen, {Cecilie Bo} and Charlotte Helgstrand and {Rose Bjelke}, Jais and Finn Matthiesen and Nielsen, {Susanne Dam} and Iversen, {Kasper Karmark} and Ostrowski, {Sisse Rye} and Henning Bundgaard and Ruth Frikke-Schmidt and Peter Garred and Mikkel-Ole Skjoedt",
note = "Copyright {\textcopyright} 2021 Bayarri-Olmos, Jarlhelt, Johnsen, Hansen, Helgstrand, Rose Bjelke, Matthiesen, Nielsen, Iversen, Ostrowski, Bundgaard, Frikke-Schmidt, Garred and Skjoedt.",
year = "2021",
month = oct,
day = "7",
doi = "10.3389/fimmu.2021.757197",
language = "English",
volume = "12",
pages = "757197",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants

AU - Bayarri-Olmos, Rafael

AU - Jarlhelt, Ida

AU - Johnsen, Laust Bruun

AU - Hansen, Cecilie Bo

AU - Helgstrand, Charlotte

AU - Rose Bjelke, Jais

AU - Matthiesen, Finn

AU - Nielsen, Susanne Dam

AU - Iversen, Kasper Karmark

AU - Ostrowski, Sisse Rye

AU - Bundgaard, Henning

AU - Frikke-Schmidt, Ruth

AU - Garred, Peter

AU - Skjoedt, Mikkel-Ole

N1 - Copyright © 2021 Bayarri-Olmos, Jarlhelt, Johnsen, Hansen, Helgstrand, Rose Bjelke, Matthiesen, Nielsen, Iversen, Ostrowski, Bundgaard, Frikke-Schmidt, Garred and Skjoedt.

PY - 2021/10/7

Y1 - 2021/10/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85117569426&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2021.757197

DO - 10.3389/fimmu.2021.757197

M3 - Journal article

C2 - 34691078

VL - 12

SP - 757197

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 757197

ER -

ID: 68661687