Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron.
Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron.
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DOI：
10.1016/j.cell.2022.01.019
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发表时间：
2022-03-03
期刊：
影响因子：
64.5
通讯作者：
Wang X
中科院分区：
文献类型：
--
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
适应性增强的SARS-CoV-2 Omicron变种正在全球范围内迅速传播。对来自Omicron的刺突（S）的cryo-EM结构的分析表明，氨基酸取代形成相互作用，稳定地保持受体识别的活性构象。相对更紧凑的结构域组织赋予改进的稳定性并增强附着，但损害病毒融合步骤的效率。局部构象、电荷和疏水微环境的改变支持表位的调节，使得它们不被大多数NTD和RBD抗体识别，从而促进病毒免疫逃逸。与人ACE 2结合的Omicron S的结构，以及对25种肉瘤病毒成员ACE 2结合区序列保守性的分析，以及免疫原性位点及其相应突变频率的热图，揭示了可用于开发广谱疫苗和治疗剂的保守和结构限制区域。SARS-CoV-2 Omicron变异体中的突变提高了支持病毒附着的刺突三聚体稳定性，但似乎损害了病毒融合。它们还干扰抗体识别的抗原位点的确认，这可能有助于免疫逃避。
The SARS-CoV-2 Omicron variant with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM 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. Mutations in the SARS-CoV-2 Omicron variant improve spike trimer stability that supports viral attachment but appears to compromise viral fusion. They also perturb the confirmation of antigenic sites for antibody recognition, which may contribute to immune evasion.
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影响因子：
48
作者：
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通讯作者：
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影响因子：
64.8
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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
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SARS-COV-2血统的估计可传播和影响B.1.1.7在英国。
DOI：
10.1126/science.abg3055
发表时间：
2021-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Davies NG;Abbott S;Barnard RC;Jarvis CI;Kucharski AJ;Munday JD;Pearson CAB;Russell TW;Tully DC;Washburne AD;Wenseleers T;Gimma A;Waites W;Wong KLM;van Zandvoort K;Silverman JD;CMMID COVID-19 Working Group;COVID-19 Genomics UK (COG-UK) Consortium;Diaz-Ordaz K;Keogh R;Eggo RM;Funk S;Jit M;Atkins KE;Edmunds WJ
通讯作者：
Edmunds WJ
影响因子：
64.5
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Screaton GR
影响因子：
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