Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants
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Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants. / Bayarri-Olmos, Rafael; Jarlhelt, Ida; Johnsen, Laust Bruun; Hansen, Cecilie Bo; Helgstrand, Charlotte; Rose Bjelke, Jais; Matthiesen, Finn; Nielsen, Susanne Dam; Iversen, Kasper Karmark; Ostrowski, Sisse Rye; Bundgaard, Henning; Frikke-Schmidt, Ruth; Garred, Peter; Skjoedt, Mikkel Ole.
In: Frontiers in Immunology, Vol. 12, 757197, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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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 - Publisher Copyright: © Copyright © 2021 Bayarri-Olmos, Jarlhelt, Johnsen, Hansen, Helgstrand, Rose Bjelke, Matthiesen, Nielsen, Iversen, Ostrowski, Bundgaard, Frikke-Schmidt, Garred and Skjoedt.
PY - 2021
Y1 - 2021
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.
KW - ACE-2
KW - B.1.351
KW - E484K
KW - N501Y
KW - P.1
KW - RBD
KW - SARS-CoV-2
KW - variant of concern
U2 - 10.3389/fimmu.2021.757197
DO - 10.3389/fimmu.2021.757197
M3 - Journal article
C2 - 34691078
AN - SCOPUS:85117569426
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 757197
ER -
ID: 284198043