Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 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 G6...

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Autores principales:	Sten Ilmjärv, Fabien Abdul, Silvia Acosta-Gutiérrez, Carolina Estarellas, Ioannis Galdadas, Marina Casimir, Marco Alessandrini, Francesco Luigi Gervasio, Karl-Heinz Krause
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/425fb19c933a4ad18acbebcbf3e961d0
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spelling	oai:doaj.org-article:425fb19c933a4ad18acbebcbf3e961d02021-12-02T18:18:58ZConcurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant10.1038/s41598-021-91662-w2045-2322https://doaj.org/article/425fb19c933a4ad18acbebcbf3e961d02021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91662-whttps://doaj.org/toc/2045-2322Abstract 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.Sten IlmjärvFabien AbdulSilvia Acosta-GutiérrezCarolina EstarellasIoannis GaldadasMarina CasimirMarco AlessandriniFrancesco Luigi GervasioKarl-Heinz KrauseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sten Ilmjärv Fabien Abdul Silvia Acosta-Gutiérrez Carolina Estarellas Ioannis Galdadas Marina Casimir Marco Alessandrini Francesco Luigi Gervasio Karl-Heinz Krause Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant
description	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.
format	article
author	Sten Ilmjärv Fabien Abdul Silvia Acosta-Gutiérrez Carolina Estarellas Ioannis Galdadas Marina Casimir Marco Alessandrini Francesco Luigi Gervasio Karl-Heinz Krause
author_facet	Sten Ilmjärv Fabien Abdul Silvia Acosta-Gutiérrez Carolina Estarellas Ioannis Galdadas Marina Casimir Marco Alessandrini Francesco Luigi Gervasio Karl-Heinz Krause
author_sort	Sten Ilmjärv
title	Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant
title_short	Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant
title_full	Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant
title_fullStr	Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant
title_full_unstemmed	Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant
title_sort	concurrent mutations in rna-dependent rna polymerase and spike protein emerged as the epidemiologically most successful sars-cov-2 variant
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/425fb19c933a4ad18acbebcbf3e961d0
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Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant

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