1. Atypical Mutational Spectrum of SARS-CoV-2 Replicating in the Presence of Ribavirin
- Author
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Pilar Somovilla, Carlos García-Crespo, Brenda Martínez-González, María Eugenia Soria, Ana Isabel de Ávila, Isabel Gallego, Pablo Mínguez, Antoni Durán-Pastor, Cristina Ferrer-Orta, Llanos Salar-Vidal, Mario Esteban-Muñoz, Sonia Zuñiga, Isabel Sola, Luis Enjuanes, Jaime Esteban, Ricardo Fernandez-Roblas, Ignacio Gadea, Jordi Gómez, Nuria Verdaguer, Esteban Domingo, and Celia Perales
- Subjects
Pharmacology ,Infectious Diseases ,Pharmacology (medical) - Abstract
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.
- Published
- 2023