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

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作者
Sandra Isabel
Lucía Graña-Miraglia
Jahir M. Gutierrez
Cedoljub Bundalovic-Torma
Helen E. Groves
Marc R. Isabel
AliReza Eshaghi
Samir N. Patel
Jonathan B. Gubbay
Tomi Poutanen
David S. Guttman
Susan M. Poutanen
机构
[1] University of Toronto,Infectious Diseases Division, Department of Paediatrics, The Hospital for Sick Children
[2] University of Toronto,Centre for the Analysis of Genome Evolution and Function
[3] University of Toronto,Department of Cell and Systems Biology
[4] Université Laval,Département de mathématique
[5] Public Health Ontario,Department of Laboratory Medicine and Pathobiology
[6] University of Toronto,Department of Medicine
[7] University of Toronto,Department of Microbiology
[8] University Health System/Sinai Health,undefined
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Scientific Reports | / 10卷
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摘要
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.
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