tetano
Editor, Senior Moderator
Immunity
. 2021 Jun 8;S1074-7613(21)00247-8.
doi: 10.1016/j.immuni.2021.06.003. Online ahead of print.
Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species
Ruoke Wang[SUP] 1 [/SUP], Qi Zhang[SUP] 2 [/SUP], Jiwan Ge[SUP] 3 [/SUP], Wenlin Ren[SUP] 4 [/SUP], Rui Zhang[SUP] 2 [/SUP], Jun Lan[SUP] 3 [/SUP], Bin Ju[SUP] 5 [/SUP], Bin Su[SUP] 6 [/SUP], Fengting Yu[SUP] 7 [/SUP], Peng Chen[SUP] 2 [/SUP], Huiyu Liao[SUP] 6 [/SUP], Yingmei Feng[SUP] 6 [/SUP], Xuemei Li[SUP] 6 [/SUP], Xuanling Shi[SUP] 2 [/SUP], Zheng Zhang[SUP] 5 [/SUP], Fujie Zhang[SUP] 7 [/SUP], Qiang Ding[SUP] 4 [/SUP], Tong Zhang[SUP] 8 [/SUP], Xinquan Wang[SUP] 9 [/SUP], Linqi Zhang[SUP] 10 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge during the global pandemic and may facilitate escape from current antibody therapies and vaccine protection. Here we showed that the South African variant B.1.351 was the most resistant to current monoclonal antibodies and convalescent plasma from coronavirus disease 2019 (COVID-19)-infected individuals, followed by the Brazilian variant P.1 and the United Kingdom variant B.1.1.7. This resistance hierarchy corresponded with Y144del and 242-244del mutations in the N-terminal domain and K417N/T, E484K, and N501Y mutations in the receptor-binding domain (RBD) of SARS-CoV-2. Crystal structure analysis of the B.1.351 triple mutant (417N-484K-501Y) RBD complexed with the monoclonal antibody P2C-1F11 revealed the molecular basis for antibody neutralization and escape. B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry. Our results demonstrate major antigenic shifts and potential broadening of the host range for B.1.351 and P.1 variants, which poses serious challenges to current antibody therapies and vaccine protection.
Keywords: SARS-CoV-2; antibody; immune escape; neutralization; variant of concern.
. 2021 Jun 8;S1074-7613(21)00247-8.
doi: 10.1016/j.immuni.2021.06.003. Online ahead of print.
Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species
Ruoke Wang[SUP] 1 [/SUP], Qi Zhang[SUP] 2 [/SUP], Jiwan Ge[SUP] 3 [/SUP], Wenlin Ren[SUP] 4 [/SUP], Rui Zhang[SUP] 2 [/SUP], Jun Lan[SUP] 3 [/SUP], Bin Ju[SUP] 5 [/SUP], Bin Su[SUP] 6 [/SUP], Fengting Yu[SUP] 7 [/SUP], Peng Chen[SUP] 2 [/SUP], Huiyu Liao[SUP] 6 [/SUP], Yingmei Feng[SUP] 6 [/SUP], Xuemei Li[SUP] 6 [/SUP], Xuanling Shi[SUP] 2 [/SUP], Zheng Zhang[SUP] 5 [/SUP], Fujie Zhang[SUP] 7 [/SUP], Qiang Ding[SUP] 4 [/SUP], Tong Zhang[SUP] 8 [/SUP], Xinquan Wang[SUP] 9 [/SUP], Linqi Zhang[SUP] 10 [/SUP]
Affiliations
- PMID: 34166623
- DOI: 10.1016/j.immuni.2021.06.003
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge during the global pandemic and may facilitate escape from current antibody therapies and vaccine protection. Here we showed that the South African variant B.1.351 was the most resistant to current monoclonal antibodies and convalescent plasma from coronavirus disease 2019 (COVID-19)-infected individuals, followed by the Brazilian variant P.1 and the United Kingdom variant B.1.1.7. This resistance hierarchy corresponded with Y144del and 242-244del mutations in the N-terminal domain and K417N/T, E484K, and N501Y mutations in the receptor-binding domain (RBD) of SARS-CoV-2. Crystal structure analysis of the B.1.351 triple mutant (417N-484K-501Y) RBD complexed with the monoclonal antibody P2C-1F11 revealed the molecular basis for antibody neutralization and escape. B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry. Our results demonstrate major antigenic shifts and potential broadening of the host range for B.1.351 and P.1 variants, which poses serious challenges to current antibody therapies and vaccine protection.
Keywords: SARS-CoV-2; antibody; immune escape; neutralization; variant of concern.