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Site-specific glycan analysis of the SARS-CoV-2 spike
Science ( IF 56.9 ) Pub Date : 2020-05-04 , DOI: 10.1126/science.abb9983
Yasunori Watanabe 1, 2, 3 , Joel D Allen 1 , Daniel Wrapp 4 , Jason S McLellan 4 , Max Crispin 1
Affiliation  

SARS-CoV-2 spike protein, elaborated Vaccine development for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on the trimeric spike protein that initiates infection. Each protomer in the trimeric spike has 22 glycosylation sites. How these sites are glycosylated may affect which cells the virus can infect and could shield some epitopes from antibody neutralization. Watanabe et al. expressed and purified recombinant glycosylated spike trimers, proteolysed them to yield glycopeptides containing a single glycan, and determined the composition of the glycan sites by mass spectrometry. The analysis provides a benchmark that can be used to measure antigen quality as vaccines and antibody tests are developed. Science this issue p. 330 A mass spectrometry analysis reveals the glycan composition at all glycosylation sites on the SARS-CoV-2 spike protein. The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion. The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.

中文翻译:

SARS-CoV-2 尖峰的位点特异性聚糖分析

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 疫苗开发的重点是引发感染的三聚体刺突蛋白。三聚体刺突中的每个原体都有 22 个糖基化位点。这些位点如何糖基化可能会影响病毒可以感染哪些细胞,并可以保护某些表位免受抗体中和。渡边等人。表达和纯化重组糖基化刺突三聚体,将它们蛋白水解以产生含有单个聚糖的糖肽,并通过质谱法确定聚糖位点的组成。该分析提供了一个基准,可用于在开发疫苗和抗体测试时测量抗原质量。科学这个问题 p。330 质谱分析揭示了 SARS-CoV-2 刺突蛋白上所有糖基化位点的聚糖组成。β冠状病毒、严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的出现是 2019 年冠状病毒病 (COVID-19) 的病原体,对全球人类健康构成了相当大的威胁。疫苗开发的重点是体液免疫反应的主要目标,即介导细胞进入和膜融合的刺突 (S) 糖蛋白。SARS-CoV-2 S 基因为每个原聚体编码 22 个 N 连接的聚糖序列,这可能在蛋白质折叠和免疫逃避中发挥作用。在这里,我们使用位点特异性质谱方法揭示了重组 SARS-CoV-2 S 免疫原上的聚糖结构。这种分析能够映射三聚体病毒尖峰中的聚糖加工状态。我们展示了 SARS-CoV-2 S 聚糖与典型宿主聚糖加工的不同之处,这可能对病毒病理生物学和疫苗设计产生影响。
更新日期:2020-05-04
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