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SARS-CoV-2 D614G 刺突蛋白突变的进化和结构分析现已在全球范围内记录。

Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide.

机构信息

Infectious Diseases Division, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, ON, Canada.

出版信息

Sci Rep. 2020 Aug 20;10(1):14031. doi: 10.1038/s41598-020-70827-z.

DOI:10.1038/s41598-020-70827-z
PMID:32820179
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7441380/
Abstract

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10-25 January) 2020. We also applied structural bioinformatics to assess the potential impact of D614G on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.

摘要

新型冠状病毒病(COVID-19)是由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起的,世界卫生组织于 2020 年 3 月 11 日宣布。根据约翰霍普金斯大学的数据,截至 2020 年 5 月 31 日,全球已诊断出超过 600 万例 COVID-19 病例,超过 37 万人死亡。迄今为止,已经对数千种 SARS-CoV-2 株进行了测序,为在全球范围内研究病毒的进化提供了宝贵的机会。我们对从 2019 年 12 月底到 2020 年 3 月中旬的 1225 多个 SARS-CoV-2 基因组进行了系统发育分析。我们在 SARS-CoV-2 的刺突蛋白中发现了一个错义突变 D614G,该突变已成为欧洲的主要分支(1449 个序列中的 954 个(66%)),并在全球范围内传播(2795 个序列中的 1237 个(44%))。分子定年分析估计该分支大约在 2020 年 1 月中旬至下旬(1 月 10 日至 25 日)出现。我们还应用结构生物信息学来评估 D614G 对 SARS-CoV-2 毒力和流行病学的潜在影响。对刺突蛋白结构的计算机模拟分析表明,该突变对蛋白质功能的影响很可能是中性的,因为它与该蛋白与人类 ACE2 受体的相互作用有关。缺乏可用的临床元数据使我们无法调查病毒分支与疾病严重程度表型之间的关系。未来需要利用病毒和人类基因组多样性的临床结果数据进行监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f13/7441380/9d8f5356466c/41598_2020_70827_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f13/7441380/67c7fe89ba22/41598_2020_70827_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f13/7441380/9ae4476e09c3/41598_2020_70827_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f13/7441380/5f79e77e7dbd/41598_2020_70827_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f13/7441380/9d8f5356466c/41598_2020_70827_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f13/7441380/67c7fe89ba22/41598_2020_70827_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f13/7441380/9ae4476e09c3/41598_2020_70827_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f13/7441380/5f79e77e7dbd/41598_2020_70827_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f13/7441380/9d8f5356466c/41598_2020_70827_Fig4_HTML.jpg

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