Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species

Wang，Ruoke1,2; Zhang，Qi1; Ge，Jiwan3; Ren，Wenlin4,5; Zhang，Rui1; Lan，Jun3; Ju，Bin6,7; Su，Bin8; Yu，Fengting9; Chen，Peng1; Liao，Huiyu8; Feng，Yingmei8; Li，Xuemei8; Shi，Xuanling1; Zhang，Zheng6,7; Zhang，Fujie9; Ding，Qiang4,5; Zhang，Tong8; Wang，Xinquan3; Zhang，Linqi1,10,11

2021

10.1016/j.immuni.2021.06.003

IMMUNITY   影响因子和分区

1074-7613

1097-4180

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.

antibody immune escape neutralization SARS-CoV-2 variant of concern

SCI

英语

NI论文 ; ESI高被引

其他

WOS:000672812100021

IMMUNOLOGY

2-s2.0-85108562925

Scopus

1.NexVac Research Center,Comprehensive AIDS Research Center,Center for Infectious Disease Research,Beijing Advanced Innovation Center for Structural Biology,School of Medicine,Tsinghua University,Beijing,100084,China
2.Tsinghua-Peking Joint Center for Life Sciences,Beijing,100084,China
3.The Ministry of Education Key Laboratory of Protein Science,Beijing Advanced Innovation Center for Structural Biology,Beijing Frontier Research Center for Biological Structure,Collaborative Innovation Center for Biotherapy,School of Life Sciences,Tsinghua University,Beijing,100084,China
4.Center for Infectious Disease Research,School of Medicine,Tsinghua University,Beijing,100084,China
5.Beijing Advanced Innovation Center for Structural Biology,Tsinghua University,Beijing,100084,China
6.Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital; The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,518112,China
7.The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,China
8.Beijing Youan Hospital,Capital Medical University,Beijing,100069,China
9.Clinical and Research Center of Infectious Diseases,Beijing Ditan Hospital,Capital Medical University,Chaoyang,No. 8, Jing Shun Dong Jie, District Beijing,100015,China
10.Institute of Biopharmaceutical and Health Engineering,Tsinghua Shenzhen International Graduate School,Tsinghua University,Shenzhen,518055,China
11.Institute of Biomedical Health Technology and Engineering,Shenzhen Bay Laboratory,Shenzhen,518132,China

Wang，Ruoke,Zhang，Qi,Ge，Jiwan,et al. Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species[J]. IMMUNITY,2021.

Wang，Ruoke.,Zhang，Qi.,Ge，Jiwan.,Ren，Wenlin.,Zhang，Rui.,...&Zhang，Linqi.(2021).Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species.IMMUNITY.

Wang，Ruoke,et al."Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species".IMMUNITY (2021).