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 m...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2023-01, Vol.67 (1), p.e0131522
Main Authors: Somovilla, Pilar, García-Crespo, Carlos, Martínez-González, Brenda, Soria, María Eugenia, de Ávila, Ana Isabel, Gallego, Isabel, Mínguez, Pablo, Durán-Pastor, Antoni, Ferrer-Orta, Cristina, Salar-Vidal, Llanos, Esteban-Muñoz, Mario, Zuñiga, Sonia, Sola, Isabel, Enjuanes, Luis, Esteban, Jaime, Fernandez-Roblas, Ricardo, Gadea, Ignacio, Gómez, Jordi, Verdaguer, Nuria, Domingo, Esteban, Perales, Celia
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents
Antiviral Agents - pharmacology
Antiviral Agents - therapeutic use
Chlorocebus aethiops
COVID-19
Mutagens - pharmacology
Mutation
Ribavirin - pharmacology
Ribavirin - therapeutic use
SARS-CoV-2 - genetics
Vero Cells
Virology
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Summary: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.
ISSN:0066-4804
1098-6596
DOI:10.1128/aac.01315-22