Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide
Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide
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DOI：
10.1038/s41598-020-70827-z
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发表时间：
2020-08-20
影响因子：
4.6
通讯作者：
Poutanen, Susan M.
中科院分区：
文献类型：
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作者：
Isabel, Sandra;Grana-Miraglia, Lucia;Poutanen, Susan M.
世界卫生组织于2020年3月11日宣布，由严重急性呼吸综合征冠状病毒2号引起的新冠肺炎大流行。根据约翰·霍普金斯大学的数据，截至2020年5月31日，全球已有600多万例新冠肺炎确诊病例，超过37万人死亡。到目前为止，已对数千株SARS-CoV-2毒株进行了测序，这为在全球范围内调查该病毒的进化提供了宝贵的机会。我们对2019年12月下旬至2020年3月中旬超过1225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，它已经成为欧洲的一个主要分支(1449个序列中的954个(66%))，并在世界各地传播(2795个序列中的1237个(44%))。分子测年分析估计，这一分支的出现大约在2020年1月中下旬(1月10日至25日)。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。在电子计算机中，对Spike蛋白结构的分析表明，该突变很可能对蛋白质功能没有影响，因为它与人ACE2受体的相互作用有关。缺乏可用的临床数据阻碍了我们对病毒分支和疾病严重程度表型之间的相关性的研究。未来的工作需要利用病毒和人类基因组多样性的临床结果数据来监测大流行。
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.