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Favipiravir Suppresses Zika Virus (ZIKV) through Activity as a Mutagen
In a companion paper, we demonstrated that the nucleoside analogue favipiravir (FAV) suppressed Zika virus (ZIKV) replication in three human-derived cell lines—HeLa, SK-N-MC, and HUH-7. Our results revealed that FAV’s effect was most pronounced in HeLa cells. In this work, we aimed to explain variat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10224157/ https://www.ncbi.nlm.nih.gov/pubmed/37317316 http://dx.doi.org/10.3390/microorganisms11051342 |
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author | Franco, Evelyn J. Cella, Eleonora Tao, Xun Hanrahan, Kaley C. Azarian, Taj Brown, Ashley N. |
author_facet | Franco, Evelyn J. Cella, Eleonora Tao, Xun Hanrahan, Kaley C. Azarian, Taj Brown, Ashley N. |
author_sort | Franco, Evelyn J. |
collection | PubMed |
description | In a companion paper, we demonstrated that the nucleoside analogue favipiravir (FAV) suppressed Zika virus (ZIKV) replication in three human-derived cell lines—HeLa, SK-N-MC, and HUH-7. Our results revealed that FAV’s effect was most pronounced in HeLa cells. In this work, we aimed to explain variation in FAV activity, investigating its mechanism of action and characterizing host cell factors relevant to tissue-specific differences in drug effect. Using viral genome sequencing, we show that FAV therapy was associated with an increase in the number of mutations and promoted the production of defective viral particles in all three cell lines. Our findings demonstrate that defective viral particles made up a larger portion of the viral population released from HeLa cells both at increasing FAV concentrations and at increasing exposure times. Taken together, our companion papers show that FAV acts via lethal mutagenesis against ZIKV and highlight the host cell’s influence on the activation and antiviral activity of nucleoside analogues. Furthermore, the information gleaned from these companion papers can be applied to gain a more comprehensive understanding of the activity of nucleoside analogues and the impact of host cell factors against other viral infections for which we currently have no approved antiviral therapies. |
format | Online Article Text |
id | pubmed-10224157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102241572023-05-28 Favipiravir Suppresses Zika Virus (ZIKV) through Activity as a Mutagen Franco, Evelyn J. Cella, Eleonora Tao, Xun Hanrahan, Kaley C. Azarian, Taj Brown, Ashley N. Microorganisms Article In a companion paper, we demonstrated that the nucleoside analogue favipiravir (FAV) suppressed Zika virus (ZIKV) replication in three human-derived cell lines—HeLa, SK-N-MC, and HUH-7. Our results revealed that FAV’s effect was most pronounced in HeLa cells. In this work, we aimed to explain variation in FAV activity, investigating its mechanism of action and characterizing host cell factors relevant to tissue-specific differences in drug effect. Using viral genome sequencing, we show that FAV therapy was associated with an increase in the number of mutations and promoted the production of defective viral particles in all three cell lines. Our findings demonstrate that defective viral particles made up a larger portion of the viral population released from HeLa cells both at increasing FAV concentrations and at increasing exposure times. Taken together, our companion papers show that FAV acts via lethal mutagenesis against ZIKV and highlight the host cell’s influence on the activation and antiviral activity of nucleoside analogues. Furthermore, the information gleaned from these companion papers can be applied to gain a more comprehensive understanding of the activity of nucleoside analogues and the impact of host cell factors against other viral infections for which we currently have no approved antiviral therapies. MDPI 2023-05-19 /pmc/articles/PMC10224157/ /pubmed/37317316 http://dx.doi.org/10.3390/microorganisms11051342 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Franco, Evelyn J. Cella, Eleonora Tao, Xun Hanrahan, Kaley C. Azarian, Taj Brown, Ashley N. Favipiravir Suppresses Zika Virus (ZIKV) through Activity as a Mutagen |
title | Favipiravir Suppresses Zika Virus (ZIKV) through Activity as a Mutagen |
title_full | Favipiravir Suppresses Zika Virus (ZIKV) through Activity as a Mutagen |
title_fullStr | Favipiravir Suppresses Zika Virus (ZIKV) through Activity as a Mutagen |
title_full_unstemmed | Favipiravir Suppresses Zika Virus (ZIKV) through Activity as a Mutagen |
title_short | Favipiravir Suppresses Zika Virus (ZIKV) through Activity as a Mutagen |
title_sort | favipiravir suppresses zika virus (zikv) through activity as a mutagen |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10224157/ https://www.ncbi.nlm.nih.gov/pubmed/37317316 http://dx.doi.org/10.3390/microorganisms11051342 |
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