Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant.
Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant.
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DOI：
10.1126/science.abl9463
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发表时间：
2021-12-10
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影响因子：
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了解严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）变异体的传播性和免疫逃避增加的分子机制对于指导当前和未来的干预策略至关重要。Zhang等人确定了SARS-CoV-2的Delta、Kappa和Gamma变体的全长刺突蛋白三聚体的冷冻电子显微镜结构，并研究了它们的功能和抗原特性。Delta刺突蛋白在细胞受体ACE 2的低水平下更有效地融合膜，并且其假型病毒感染靶细胞的速度比测试的所有其他变体都要快得多，这可能至少部分地解释了其高传播性。每个变体的突变重排刺突蛋白的N-末端结构域的抗原表面，但仅引起受体结合结构域的局部变化，这与对中和抗体的更大抗性一致。这些发现阐明了导致这些病毒适应人类社区并逃避宿主免疫的分子事件。-VV结构和功能研究解释了SARS-CoV-2 Delta变体的高传播性和免疫逃避。严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）的Delta变体已经超过了以前流行的变体，并成为全球的主导菌株。我们报告的结构，功能和抗原性的全长刺（S）三聚体，以及γ和κ变体，并比较其特性与G614，α和β变体。Delta S可以在细胞受体血管紧张素转换酶2（ACE 2）水平较低时更有效地融合细胞膜，其假型病毒感染靶细胞的速度比其他五种变体快得多，这可能是其传播性提高的原因。每个变体显示S蛋白的氨基末端结构域的抗原表面的不同重排，但仅使受体结合结构域（RBD）产生变化，使RBD成为治疗性抗体的更好靶点。
Understanding the molecular mechanisms of the increased transmissibility and immune evasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is critical to guiding current and future intervention strategies. Zhang et al. determined cryo–electron microscopy structures of the full-length spike protein trimers of the Delta, Kappa, and Gamma variants of SARS-CoV-2 and studied their function and antigenic properties. The Delta spike protein fused membranes more efficiently at low levels of the cellular receptor ACE2, and its pseudotyped viruses infected target cells substantially more rapidly than all other variants tested, possibly at least partly accounting for its heightened transmissibility. Mutations of each variant rearranged the antigenic surface of the N-terminal domain of the spike protein but only caused local changes in the receptor-binding domain, consistent with greater resistance to neutralizing antibodies. These findings elucidate the molecular events that have led these viruses to adapt in human communities and to evade host immunity. —VV Structural and functional studies explain the heightened transmissibility and immune evasion of the SARS-CoV-2 Delta variant. The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has outcompeted previously prevalent variants and become a dominant strain worldwide. We report the structure, function, and antigenicity of its full-length spike (S) trimer as well as those of the Gamma and Kappa variants, and compare their characteristics with the G614, Alpha, and Beta variants. Delta S can fuse membranes more efficiently at low levels of cellular receptor angiotensin converting enzyme 2 (ACE2), and its pseudotyped viruses infect target cells substantially faster than the other five variants, possibly accounting for its heightened transmissibility. Each variant shows different rearrangement of the antigenic surface of the amino-terminal domain of the S protein but only makes produces changes in the receptor binding domain (RBD), making the RBD a better target for therapeutic antibodies.
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影响因子：
48
作者：
Kucukelbir, Alp;Sigworth, Fred J.;Tagare, Hemant D.
通讯作者：
Tagare, Hemant D.
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
DOI：
10.1503/cmaj.211248
发表时间：
2021-10-25
期刊：
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne
影响因子：
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作者：
Fisman DN;Tuite AR
通讯作者：
Tuite AR
影响因子：
64.5
作者：
Hoffmann M;Arora P;Groß R;Seidel A;Hörnich BF;Hahn AS;Krüger N;Graichen L;Hofmann-Winkler H;Kempf A;Winkler MS;Schulz S;Jäck HM;Jahrsdörfer B;Schrezenmeier H;Müller M;Kleger A;Münch J;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
56.9
作者：
Cai, Yongfei;Zhang, Jun;Chen, Bing
通讯作者：
Chen, Bing