Atypical Mutational Spectrum of SARS-CoV-2 Replicating in the Presence of Ribavirin
We report that ribavirin exerts an inhibitory and mutagenic activity on SARS-CoV-2-infecting Vero cells, with a therapeutic index higher than 10. Deep sequencing analysis of the mutant spectrum of SARS-CoV-2 replicating in the absence or presence of ribavirin indicated an increase in the number of mutations, but not in deletions, and modification of diversity indices, expected from a mutagenic activity. Notably, the major mutation types enhanced by replication in the presence of ribavirin were A→G and U→C transitions, a pattern which is opposite to the dominance of G→A and C→U transitions previously described for most RNA viruses. Implications of the inhibitory activity of ribavirin, and the atypical mutational bias produced on SARS-CoV-2, for the search for synergistic anti-COVID-19 lethal mutagen combinations are discussed.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
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| Enthalten in: |
Antimicrobial agents and chemotherapy - 67(2023), 1 vom: 24. Jan., Seite e0131522 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Somovilla, Pilar [VerfasserIn] |
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| Links: |
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| Themen: |
49717AWG6K |
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| Anmerkungen: |
Date Completed 26.01.2023 Date Revised 02.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1128/aac.01315-22 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM351135227 |
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| 520 | |a We report that ribavirin exerts an inhibitory and mutagenic activity on SARS-CoV-2-infecting Vero cells, with a therapeutic index higher than 10. Deep sequencing analysis of the mutant spectrum of SARS-CoV-2 replicating in the absence or presence of ribavirin indicated an increase in the number of mutations, but not in deletions, and modification of diversity indices, expected from a mutagenic activity. Notably, the major mutation types enhanced by replication in the presence of ribavirin were A→G and U→C transitions, a pattern which is opposite to the dominance of G→A and C→U transitions previously described for most RNA viruses. Implications of the inhibitory activity of ribavirin, and the atypical mutational bias produced on SARS-CoV-2, for the search for synergistic anti-COVID-19 lethal mutagen combinations are discussed | ||
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| 700 | 1 | |a de Ávila, Ana Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Gallego, Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Mínguez, Pablo |e verfasserin |4 aut | |
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| 700 | 1 | |a Salar-Vidal, Llanos |e verfasserin |4 aut | |
| 700 | 1 | |a Esteban-Muñoz, Mario |e verfasserin |4 aut | |
| 700 | 1 | |a Zuñiga, Sonia |e verfasserin |4 aut | |
| 700 | 1 | |a Sola, Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Enjuanes, Luis |e verfasserin |4 aut | |
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