Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant
The D614G mutation in the Spike protein of the SARS-CoV-2 has effectively replaced the early pandemic-causing variant. Using pseudotyped lentivectors, we confirmed that the aspartate replacement by glycine in position 614 is markedly more infectious. Molecular modelling suggests that the G614 mutati...
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Published in | Scientific reports Vol. 11; no. 1; p. 13705 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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Nature Publishing Group UK
01.07.2021
Nature Publishing Group Nature Portfolio |
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Abstract | The D614G mutation in the Spike protein of the SARS-CoV-2 has effectively replaced the early pandemic-causing variant. Using pseudotyped lentivectors, we confirmed that the aspartate replacement by glycine in position 614 is markedly more infectious. Molecular modelling suggests that the G614 mutation facilitates transition towards an open state of the Spike protein. To explain the epidemiological success of D614G, we analysed the evolution of 27,086 high-quality SARS-CoV-2 genome sequences from GISAID. We observed striking coevolution of D614G with the P323L mutation in the viral polymerase. Importantly, the exclusive presence of G614 or L323 did not become epidemiologically relevant. In contrast, the combination of the two mutations gave rise to a viral G/L variant that has all but replaced the initial D/P variant. Our results suggest that the P323L mutation, located in the interface domain of the RNA-dependent RNA polymerase, is a necessary alteration that led to the epidemiological success of the present variant of SARS-CoV-2. However, we did not observe a significant correlation between reported COVID-19 mortality in different countries and the prevalence of the Wuhan versus G/L variant. Nevertheless, when comparing the speed of emergence and the ultimate predominance in individual countries, it is clear that the G/L variant displays major epidemiological supremacy over the original variant. |
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AbstractList | The D614G mutation in the Spike protein of the SARS-CoV-2 has effectively replaced the early pandemic-causing variant. Using pseudotyped lentivectors, we confirmed that the aspartate replacement by glycine in position 614 is markedly more infectious. Molecular modelling suggests that the G614 mutation facilitates transition towards an open state of the Spike protein. To explain the epidemiological success of D614G, we analysed the evolution of 27,086 high-quality SARS-CoV-2 genome sequences from GISAID. We observed striking coevolution of D614G with the P323L mutation in the viral polymerase. Importantly, the exclusive presence of G614 or L323 did not become epidemiologically relevant. In contrast, the combination of the two mutations gave rise to a viral G/L variant that has all but replaced the initial D/P variant. Our results suggest that the P323L mutation, located in the interface domain of the RNA-dependent RNA polymerase, is a necessary alteration that led to the epidemiological success of the present variant of SARS-CoV-2. However, we did not observe a significant correlation between reported COVID-19 mortality in different countries and the prevalence of the Wuhan versus G/L variant. Nevertheless, when comparing the speed of emergence and the ultimate predominance in individual countries, it is clear that the G/L variant displays major epidemiological supremacy over the original variant. Abstract The D614G mutation in the Spike protein of the SARS-CoV-2 has effectively replaced the early pandemic-causing variant. Using pseudotyped lentivectors, we confirmed that the aspartate replacement by glycine in position 614 is markedly more infectious. Molecular modelling suggests that the G614 mutation facilitates transition towards an open state of the Spike protein. To explain the epidemiological success of D614G, we analysed the evolution of 27,086 high-quality SARS-CoV-2 genome sequences from GISAID. We observed striking coevolution of D614G with the P323L mutation in the viral polymerase. Importantly, the exclusive presence of G614 or L323 did not become epidemiologically relevant. In contrast, the combination of the two mutations gave rise to a viral G/L variant that has all but replaced the initial D/P variant. Our results suggest that the P323L mutation, located in the interface domain of the RNA-dependent RNA polymerase, is a necessary alteration that led to the epidemiological success of the present variant of SARS-CoV-2. However, we did not observe a significant correlation between reported COVID-19 mortality in different countries and the prevalence of the Wuhan versus G/L variant. Nevertheless, when comparing the speed of emergence and the ultimate predominance in individual countries, it is clear that the G/L variant displays major epidemiological supremacy over the original variant. Abstract The D614G mutation in the Spike protein of the SARS-CoV-2 has effectively replaced the early pandemic-causing variant. Using pseudotyped lentivectors, we confirmed that the aspartate replacement by glycine in position 614 is markedly more infectious. Molecular modelling suggests that the G614 mutation facilitates transition towards an open state of the Spike protein. To explain the epidemiological success of D614G, we analysed the evolution of 27,086 high-quality SARS-CoV-2 genome sequences from GISAID. We observed striking coevolution of D614G with the P323L mutation in the viral polymerase. Importantly, the exclusive presence of G614 or L323 did not become epidemiologically relevant. In contrast, the combination of the two mutations gave rise to a viral G/L variant that has all but replaced the initial D/P variant. Our results suggest that the P323L mutation, located in the interface domain of the RNA-dependent RNA polymerase, is a necessary alteration that led to the epidemiological success of the present variant of SARS-CoV-2. However, we did not observe a significant correlation between reported COVID-19 mortality in different countries and the prevalence of the Wuhan versus G/L variant. Nevertheless, when comparing the speed of emergence and the ultimate predominance in individual countries, it is clear that the G/L variant displays major epidemiological supremacy over the original variant. |
ArticleNumber | 13705 |
Author | Casimir, Marina Alessandrini, Marco Acosta-Gutiérrez, Silvia Galdadas, Ioannis Estarellas, Carolina Krause, Karl-Heinz Abdul, Fabien Ilmjärv, Sten Gervasio, Francesco Luigi |
Author_xml | – sequence: 1 givenname: Sten surname: Ilmjärv fullname: Ilmjärv, Sten organization: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva – sequence: 2 givenname: Fabien surname: Abdul fullname: Abdul, Fabien organization: Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva – sequence: 3 givenname: Silvia surname: Acosta-Gutiérrez fullname: Acosta-Gutiérrez, Silvia organization: Department of Chemistry, University College London, Institute for the Physics of Living Systems, University College London, Institute of Structural and Molecular Biology, University College London – sequence: 4 givenname: Carolina surname: Estarellas fullname: Estarellas, Carolina organization: Department of Chemistry, University College London – sequence: 5 givenname: Ioannis surname: Galdadas fullname: Galdadas, Ioannis organization: Department of Chemistry, University College London – sequence: 6 givenname: Marina surname: Casimir fullname: Casimir, Marina organization: Neurix SA – sequence: 7 givenname: Marco surname: Alessandrini fullname: Alessandrini, Marco organization: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva – sequence: 8 givenname: Francesco Luigi surname: Gervasio fullname: Gervasio, Francesco Luigi organization: Department of Chemistry, University College London, Institute of Structural and Molecular Biology, University College London, School of Pharmaceutical Sciences, University of Geneva, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva – sequence: 9 givenname: Karl-Heinz surname: Krause fullname: Krause, Karl-Heinz email: karl-heinz.krause@unige.ch organization: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Division of Infectious Disease and Department of Diagnostics, Geneva University Hospitals |
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Snippet | The D614G mutation in the Spike protein of the SARS-CoV-2 has effectively replaced the early pandemic-causing variant. Using pseudotyped lentivectors, we... Abstract The D614G mutation in the Spike protein of the SARS-CoV-2 has effectively replaced the early pandemic-causing variant. Using pseudotyped lentivectors,... Abstract The D614G mutation in the Spike protein of the SARS-CoV-2 has effectively replaced the early pandemic-causing variant. Using pseudotyped lentivectors,... |
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Title | Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant |
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