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

Article Article scientifique Article Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant eng 2021-07-01 2021-07-01 author Ilmjarv Sten 830426 author Abdul Fabien 806185 author Acosta Gutierrez Silvia 975994 author Estarellas Martin Carolina 947498 author Galdadas Ioannis author Casimir Marina Shamini 518566 author Alessandrini Marco 0000-0002-1820-2175 856324 author Gervasio Francesco Luigi 0000-0003-4831-5039 931636 author Krause Karl-Heinz 23022 13705 10.1038/s41598-021-91662-w 34210996 2045-2322 PMC8249556 http://www.nature.com/articles/s41598-021-91662-w 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. Dewey 610 Dewey 615 Dewey 616 Dewey 616.07 31 Section des sciences pharmaceutiques 17 54 Département de microbiologie et médecine moléculaire 21B 137 Département de pathologie et immunologie 21F 50 Section de médecine clinique 22 false 1362 Modélisation biomoléculaire et pharmaceutique 38 Radicaux libres et cellules souches embryonnaires 60 Scientific reports 11 1 5839a579-d9c0-45cd-8229-02604a185091 Article (Published version) Public Article-scientifique-from-unpaywall.pdf 2612800 application/pdf CC BY-4.0 openAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique

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Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant	Scientific reports			2021	265	141

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Acosta Gutierrez, Silvia