Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants.
Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants.
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DOI：
10.1126/science.abi9745
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发表时间：
2021-08-06
期刊：
影响因子：
56.9
通讯作者：
Chen, Bing
中科院分区：
文献类型：
--
作者：
Cai, Yongfei;Zhang, Jun;Xiao, Tianshu;Lavine, Christy L.;Rawson, Shaun;Peng, Hanqin;Zhu, Haisun;Anand, Krishna;Tong, Pei;Gautam, Avneesh;Lu, Shen;Sterling, Sarah M.;Walsh, Richard M.;Rits-Volloch, Sophia;Lu, Jianming;Wesemann, Duane R.;Yang, Wei;Seaman, Michael S.;Chen, Bing
随着遏制COVID-19大流行的战斗继续进行，人们的注意力集中在严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）病毒的新变种上，这些变种被认为是令人关注的变种，因为它们对感染或疫苗接种引起的抗体具有抗性，或者它们增加了传播性或疾病的严重程度。三篇论文使用功能和结构研究来探索病毒刺突蛋白的突变如何影响其感染宿主细胞和逃避宿主免疫的能力。Gobeil等人研究了一种参与水貂和人类之间传播的变异刺突蛋白，以及B1.1.7（alpha），B.1.351（beta）和P1（gamma）刺突变体; Cai等人专注于alpha和beta变体; McCallum等人讨论了来自B1.1.427/B.1.429（beta）变体的刺突蛋白的特性。总之，这些论文显示了增强稳定性的突变之间的平衡，那些增加与人类受体ACE 2结合的突变，以及那些赋予中和抗体抗性的突变。-VV SARS-CoV-2变异体如何获得增强的感染性并逃避宿主免疫反应。严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）的几种快速传播变体已成为COVID-19大流行中的主要流行毒株。我们在此报告了B.1.1.7和B.1.351变体的全长刺突（S）三聚体的冷冻电子显微镜结构，以及它们的生物化学和抗原特性。B.1.1.7蛋白中的氨基酸取代增加了其受体结合结构域的可及性和对受体血管紧张素转换酶2（ACE 2）的结合亲和力。增强的受体结合可以解释增加的传递性。B.1.351变体已经进化为重塑S蛋白上主要中和位点的抗原表面，使其对一些有效的中和抗体具有抗性。这些发现提供了SARS-CoV-2如何进化以增强病毒适应性和免疫逃避的结构细节。
As battles to contain the COVID-19 pandemic continue, attention is focused on emerging variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that have been deemed variants of concern because they are resistant to antibodies elicited by infection or vaccination or they increase transmissibility or disease severity. Three papers used functional and structural studies to explore how mutations in the viral spike protein affect its ability to infect host cells and to evade host immunity. Gobeil et al. looked at a variant spike protein involved in transmission between minks and humans, as well as the B1.1.7 (alpha), B.1.351 (beta), and P1 (gamma) spike variants; Cai et al. focused on the alpha and beta variants; and McCallum et al. discuss the properties of the spike protein from the B1.1.427/B.1.429 (epsilon) variant. Together, these papers show a balance among mutations that enhance stability, those that increase binding to the human receptor ACE2, and those that confer resistance to neutralizing antibodies. —VV How SARS-CoV-2 variants gain enhanced infectivity and evade host immune responses. Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the dominant circulating strains in the COVID-19 pandemic. We report here cryo–electron microscopy structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Amino acid substitutions in the B.1.1.7 protein increase both the accessibility of its receptor binding domain and the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement may account for the increased transmissibility. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein, making it resistant to some potent neutralizing antibodies. These findings provide structural details on how SARS-CoV-2 has evolved to enhance viral fitness and immune evasion.
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BNT162B2 mRNA COVID-19疫苗的安全性和功效。
DOI：
10.1056/nejmoa2034577
发表时间：
2020-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
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通讯作者：
C4591001 Clinical Trial Group
影响因子：
56.9
作者：
Cai, Yongfei;Zhang, Jun;Chen, Bing
通讯作者：
Chen, Bing
影响因子：
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DOI：
10.1073/pnas.1407087111
发表时间：
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影响因子：
11.1
作者：
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通讯作者：
Whittaker, Gary R.
影响因子：
48
作者：
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通讯作者：
Brubaker, Marcus A.