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

Sandra Isabel; Lucía Graña-Miraglia; Jahir M. Gutierrez; Cedoljub Bundalovic-Torma; Helen E. Groves; Marc R. Isabel; Ali Reza Eshaghi; Samir N. Patel; Jonathan B. Gubbay; Tomi Poutanen; David S. Guttman; Susan M. Poutanen

doi:10.1038/s41598-020-70827-z

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

Sandra Isabel^*, Lucía Graña-Miraglia, Jahir M. Gutierrez, Cedoljub Bundalovic-Torma, Helen E. Groves, Marc R. Isabel, Ali Reza Eshaghi, Samir N. Patel, Jonathan B. Gubbay, Tomi Poutanen, David S. Guttman, Susan M. Poutanen

^*Corresponding author for this work

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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.

Original language	English
Article number	14031
Number of pages	9
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-70827-z
Publication status	Published - 01 Dec 2020

Bibliographical note

Funding Information:
We are very grateful to Dr William P. Hanage for his expert comments and advice on the preparation of this manuscript. We would like to thank Manon Tetreault for data collection. We are grateful to the numerous scientists who have shared their genome data with the world on GISAID (Supplementary data Table3). Funding was provided by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada Collaborative Health Research Project Grant [CP-151952] and Public Health Ontario.

Publisher Copyright:
© 2020, The Author(s).

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Evolutionary and structural analyses of SARS‑CoV‑2 D614G spike protein mutation now documented worldwide
© 2022 The Authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 2.24 MBLicence: CC BY

Cite this

Isabel, S., Graña-Miraglia, L., Gutierrez, J. M., Bundalovic-Torma, C., Groves, H. E., Isabel, M. R., Eshaghi, A. R., Patel, S. N., Gubbay, J. B., Poutanen, T., Guttman, D. S., & Poutanen, S. M. (2020). Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide. Scientific Reports, 10(1), Article 14031. https://doi.org/10.1038/s41598-020-70827-z

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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.",

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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