Academic Journal
'Outlaw' mutations in quasispecies of SARS-CoV-2 inhibit replication
| العنوان: | 'Outlaw' mutations in quasispecies of SARS-CoV-2 inhibit replication |
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| المؤلفون: | Philippe Colson, Jacques Fantini, Jeremy Delerce, Wahiba Bader, Anthony Levasseur, Pierre Pontarotti, Christian Devaux, Didier Raoult |
| المصدر: | Emerging Microbes and Infections, Vol 13, Iss 1 (2024) |
| بيانات النشر: | Taylor & Francis Group, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Infectious and parasitic diseases LCC:Microbiology |
| مصطلحات موضوعية: | SARS-CoV-2, genomics, mutations, quasispecies, evolution, next-generation sequencing, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502 |
| الوصف: | The evolution of SARS-CoV-2, the agent of COVID-19, has been remarkable for its high mutation potential, leading to the appearance of variants. Some mutations have never appeared in the published genomes, which represent consensus, or bona fide genomes. Here we tested the hypothesis that mutations that did not appear in consensus genomes were, in fact, as frequent as the mutations that appeared during the various epidemic episodes, but were not expressed because lethal. To identify these mutations, we analysed the genomes of 90 nasopharyngeal samples and the quasispecies determined by next-generation sequencing. Mutations observed in the quasispecies and not in the consensus genomes were considered to be lethal, what we called “outlaw” mutations. Among these mutations, we analysed the 21 most frequent. Eight of these “outlaws” were in the RNA polymerase and we were able to use a structural biology model and molecular dynamics simulations to demonstrate the functional incapacity of these mutated RNA polymerases. Three other mutations affected the spike, a major protein involved in the pathogenesis of COVID-19. Overall, by analysing the SARS-CoV-2 quasispecies obtained during sequencing, this method made it possible to identify “outlaws,” showing areas that could potentially become the target of treatments. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 22221751 2222-1751 |
| Relation: | https://doaj.org/toc/2222-1751 |
| DOI: | 10.1080/22221751.2024.2368211 |
| URL الوصول: | https://doaj.org/article/87097a1daa25467e8137c8798b42c197 |
| رقم الانضمام: | edsdoj.87097a1daa25467e8137c8798b42c197 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 22221751 |
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| DOI: | 10.1080/22221751.2024.2368211 |