Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron

被引：323

作者：

Cui, Zhen ^{[1
,2
]}

Liu, Pan ^{[1
,2
]}

Wang, Nan ^{[1
]}

Wang, Lei ^{[1
,2
]}

Fan, Kaiyue ^{[1
,2
]}

Zhu, Qianhui ^{[1
,2
]}

Wang, Kang ^{[1
]}

Chen, Ruihong ^{[3
]}

Feng, Rui ^{[1
]}

Jia, Zijing ^{[1
,2
]}

Yang, Minnan ^{[1
]}

Xu, Ge ^{[1
,2
]}

Zhu, Boling ^{[1
]}

Fu, Wangjun ^{[1
,2
]}

Chu, Tianming ^{[1
,2
]}

Feng, Leilei ^{[1
,2
]}

Wang, Yide ^{[1
,2
]}

Pei, Xinran ^{[1
]}

Yang, Peng ^{[1
,2
]}

Xie, Xiaoliang Sunney ^{[4
]}

Cao, Lei ^{[1
]}

Cao, Yunlong ^{[4
]}

Wang, Xiangxi ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Inst Biophys, CAS Key Lab Infect & Immun, Natl Lab Macromol, Beijing 100101, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] Guangzhou Med Univ, Guangzhou 511495, Peoples R China

[4] Peking Univ, Biomed Pioneering Innovat Ctr Biop, Beijing 100080, Peoples R China

来源：

CELL | 2022年 / 185卷 / 05期

关键词：

CRYO-EM STRUCTURE; SPIKE; ACE2; BINDING;

D O I：

10.1016/j.cell.2022.01.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The SARS-CoV-2 Omicron variant with increased fitness is spreading rapidly worldwide. Analysis of cryoEM structures of the spike (S) from Omicron reveals amino acid substitutions forging interactions that stably maintain an active conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of the viral fusion step. Alterations in local conformation, charge, and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD-and RBD-antibodies, facilitating viral immune escape. Structure of the Omicron S bound with human ACE2, together with the analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members, as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies, sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics.

引用

页码：860 / +

页数：26

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