English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/212568
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

Title

Synergistic Lethal Mutagenesis of Hepatitis C Virus

AuthorsGallego, Isabel ; Soria, María Eugenia; Gregori, Josep; de Ávila, Ana I.; García-Crespo, Carlos; Moreno, Elena ; Gadea, Ignacio; Esteban, Jaime; Fernández-Roblas, Ricardo; Esteban, Juan Ignacio; Gómez, J.; Quer, Josep; Domingo, Esteban ; Perales, Celia
Issue Date2019
PublisherAmerican Society for Microbiology
CitationAntimicrobial Agents and Chemotherapy 63 (2019)
AbstractLethal mutagenesis is an antiviral approach that consists of extinguishing a virus by an excess of mutations acquired during replication in the presence of a mutagenic agent, often a nucleotide analogue. One of its advantages is its broad-spectrum nature, which renders the strategy potentially effective against emergent RNA viral infections. Here we describe the synergistic lethal mutagenesis of hepatitis C virus (HCV) by a combination of favipiravir (T-705) and ribavirin. Synergy has been documented over a broad range of analogue concentrations using the Chou-Talalay method implemented in CompuSyn graphics software, with the average dose reduction index (DRI) being above 1 (68.02 101.6 for favipiravir and 5.83 6.07 for ribavirin) and the average combination indices (CI) being below 1 (0.52 0.28). Furthermore, analogue concentrations that individually did not extinguish high-fitness HCV in 10 serial infections extinguished high-fitness HCV in 1 to 2 passages when used in combination. Although both analogues displayed a preference for G ¡ A and C ¡ U transitions, deep sequencing analysis of mutant spectra indicated a different preference of the two analogues for the mutation sites, thus unveiling a new possible synergy mechanism in lethal mutagenesis. The prospects for synergy among mutagenic nucleotides as a strategy to confront emerging viral infections are discussed
Publisher version (URL)http://dx.doi.org/10.1128/AAC.01653-19
URIhttp://hdl.handle.net/10261/212568
DOIhttp://dx.doi.org/10.1128/AAC.01653-19
Identifiersdoi: 10.1128/AAC.01653-19
issn: 0066-4804
e-issn: 1098-6596
Appears in Collections:(CBM) Artículos
(IPBLN) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.