Structures of Omicron spike complexes and implications for neutralizing antibody development.
Structures of Omicron spike complexes and implications for neutralizing antibody development.
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Omicron 刺突复合物的结构及其对中和抗体开发的影响
DOI：
10.1016/j.celrep.2022.110770
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发表时间：
2022-05-03
期刊：
影响因子：
8.8
通讯作者：
Ji, Xiaoyun
中科院分区：
文献类型：
--
作者：
Guo, Hangtian;Gao, Yan;Li, Tinghan;Li, Tingting;Lu, Yuchi;Zheng, Le;Liu, Yue;Yang, Tingting;Luo, Feiyang;Song, Shuyi;Wang, Wei;Yang, Xiuna;Nguyen, Henry C.;Zhang, Hongkai;Huang, Ailong;Jin, Aishun;Yang, Haitao;Rao, Zihe;Ji, Xiaoyun
SARS-COV-2 OMICRON变体在全球许多国家中占主导地位。其次，我们报告了与患者衍生的Fab抗体片段结合的Omicron，delta和野生型尖峰（510a5），其中提供了直接的证据，其中抗体结合很大，由OMICRON突变大减弱，从而使Spike释放了与ACE 2的结合，并与Illy-510a相结合。抗体逃避却保留了强烈的ACE2相互作用。
Guo等人报告了ACE2结合的SARS-COV-2 OMICRON SPIKE和人类抗体（510a5）的冷冻EM结构（Omicron，delta和WT）结构清楚地说明了Omicron突变如何导致抗体演变而导致抗体进化。
The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. The high number of spike mutations is responsible for the broad immune evasion from existing vaccines and antibody drugs. To understand this, we first present the cryo-electron microscopy structure of ACE2-bound SARS-CoV-2 Omicron spike. Comparison to previous spike antibody structures explains how Omicron escapes these therapeutics. Secondly, we report structures of Omicron, Delta, and wild-type spikes bound to a patient-derived Fab antibody fragment (510A5), which provides direct evidence where antibody binding is greatly attenuated by the Omicron mutations, freeing spike to bind ACE2. Together with biochemical binding and 510A5 neutralization assays, our work establishes principles of binding required for neutralization and clearly illustrates how the mutations lead to antibody evasion yet retain strong ACE2 interactions. Structural information on spike with both bound and unbound antibodies collectively elucidates potential strategies for generation of therapeutic antibodies. Guo et al. report the cryo-EM structures of ACE2-bound SARS-CoV-2 Omicron spike and human antibody (510A5)-bound spikes of Omicron, Delta, and WT. The structures clearly illustrate how Omicron mutations lead to antibody evasion yet retain strong ACE2 interactions.
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影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
影响因子：
64.5
作者：
Cui Z;Liu P;Wang N;Wang L;Fan K;Zhu Q;Wang K;Chen R;Feng R;Jia Z;Yang M;Xu G;Zhu B;Fu W;Chu T;Feng L;Wang Y;Pei X;Yang P;Xie XS;Cao L;Cao Y;Wang X
通讯作者：
Wang X
REGN-COV2抗体预防和治疗恒河猕猴和仓鼠中的SARS-COV-2感染。
DOI：
10.1126/science.abe2402
发表时间：
2020-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Baum A;Ajithdoss D;Copin R;Zhou A;Lanza K;Negron N;Ni M;Wei Y;Mohammadi K;Musser B;Atwal GS;Oyejide A;Goez-Gazi Y;Dutton J;Clemmons E;Staples HM;Bartley C;Klaffke B;Alfson K;Gazi M;Gonzalez O;Dick E Jr;Carrion R Jr;Pessaint L;Porto M;Cook A;Brown R;Ali V;Greenhouse J;Taylor T;Andersen H;Lewis MG;Stahl N;Murphy AJ;Yancopoulos GD;Kyratsous CA
通讯作者：
Kyratsous CA
影响因子：
2.2
作者：
Chen, Shaoxia;McMullan, Greg;Faruqi, Abdul R.;Murshudov, Garib N.;Short, Judith M.;Scheres, Sjors H. W.;Henderson, Richard
通讯作者：
Henderson, Richard
影响因子：
64.5
作者：
Garcia-Beltran WF;St Denis KJ;Hoelzemer A;Lam EC;Nitido AD;Sheehan ML;Berrios C;Ofoman O;Chang CC;Hauser BM;Feldman J;Roederer AL;Gregory DJ;Poznansky MC;Schmidt AG;Iafrate AJ;Naranbhai V;Balazs AB
通讯作者：
Balazs AB