Favipiravir Inhibits Zika Virus (ZIKV) Replication in HeLa Cells by Altering Viral Infectivity
This study aims to evaluate the antiviral potential of the nucleoside analogue favipiravir (FAV) against ZIKV, an arbovirus for which there are no approved antiviral therapies, in three human-derived cell lines. HeLa (cervical), SK-N-MC (neuronal), and HUH-7 (liver) cells were infected with ZIKV and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/11/5/1097 |
| _version_ | 1827740670828216320 |
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| author | Evelyn J. Franco Kaley C. Hanrahan Ashley N. Brown |
| author_facet | Evelyn J. Franco Kaley C. Hanrahan Ashley N. Brown |
| author_sort | Evelyn J. Franco |
| collection | DOAJ |
| description | This study aims to evaluate the antiviral potential of the nucleoside analogue favipiravir (FAV) against ZIKV, an arbovirus for which there are no approved antiviral therapies, in three human-derived cell lines. HeLa (cervical), SK-N-MC (neuronal), and HUH-7 (liver) cells were infected with ZIKV and exposed to different concentrations of FAV. Viral supernatant was sampled daily, and infectious viral burden was quantified by plaque assay. Changes in ZIKV infectivity were quantified by calculating specific infectivity. FAV-related toxicities were also assessed for each cell line in both infected and uninfected cells. Our results demonstrate that FAV activity was most pronounced in HeLa cells, as substantial declines in infectious titers and viral infectivity were observed in this cell type. The decline in infectious virus occurred in an exposure-dependent manner and was more pronounced as FAV exposure times increased. Additionally, toxicity studies showed that FAV was not toxic to any of the three cell lines and, surprisingly, caused substantial improvements in the viability of infected HeLa cells. Although SK-N-MC and HUH-7 cells were susceptible to FAV’s anti-ZIKV activity, similar effects on viral infectivity and improvements in cell viability with therapy were not observed. These results indicate that FAV’s ability to substantially alter viral infectivity is host cell specific and suggest that the robust antiviral effect observed in HeLa cells is mediated through drug-induced losses of viral infectivity. |
| first_indexed | 2024-03-11T03:29:29Z |
| format | Article |
| id | doaj.art-d6c3fd94706a41cfb06ea4ce861b3807 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-11T03:29:29Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-d6c3fd94706a41cfb06ea4ce861b38072023-11-18T02:31:44ZengMDPI AGMicroorganisms2076-26072023-04-01115109710.3390/microorganisms11051097Favipiravir Inhibits Zika Virus (ZIKV) Replication in HeLa Cells by Altering Viral InfectivityEvelyn J. Franco0Kaley C. Hanrahan1Ashley N. Brown2Institute for Therapeutic Innovation, Department of Medicine, University of Florida College of Medicine, Orlando, FL 32827, USAInstitute for Therapeutic Innovation, Department of Medicine, University of Florida College of Medicine, Orlando, FL 32827, USAInstitute for Therapeutic Innovation, Department of Medicine, University of Florida College of Medicine, Orlando, FL 32827, USAThis study aims to evaluate the antiviral potential of the nucleoside analogue favipiravir (FAV) against ZIKV, an arbovirus for which there are no approved antiviral therapies, in three human-derived cell lines. HeLa (cervical), SK-N-MC (neuronal), and HUH-7 (liver) cells were infected with ZIKV and exposed to different concentrations of FAV. Viral supernatant was sampled daily, and infectious viral burden was quantified by plaque assay. Changes in ZIKV infectivity were quantified by calculating specific infectivity. FAV-related toxicities were also assessed for each cell line in both infected and uninfected cells. Our results demonstrate that FAV activity was most pronounced in HeLa cells, as substantial declines in infectious titers and viral infectivity were observed in this cell type. The decline in infectious virus occurred in an exposure-dependent manner and was more pronounced as FAV exposure times increased. Additionally, toxicity studies showed that FAV was not toxic to any of the three cell lines and, surprisingly, caused substantial improvements in the viability of infected HeLa cells. Although SK-N-MC and HUH-7 cells were susceptible to FAV’s anti-ZIKV activity, similar effects on viral infectivity and improvements in cell viability with therapy were not observed. These results indicate that FAV’s ability to substantially alter viral infectivity is host cell specific and suggest that the robust antiviral effect observed in HeLa cells is mediated through drug-induced losses of viral infectivity.https://www.mdpi.com/2076-2607/11/5/1097favipiravirZika virusantiviral therapyinfectivity |
| spellingShingle | Evelyn J. Franco Kaley C. Hanrahan Ashley N. Brown Favipiravir Inhibits Zika Virus (ZIKV) Replication in HeLa Cells by Altering Viral Infectivity Microorganisms favipiravir Zika virus antiviral therapy infectivity |
| title | Favipiravir Inhibits Zika Virus (ZIKV) Replication in HeLa Cells by Altering Viral Infectivity |
| title_full | Favipiravir Inhibits Zika Virus (ZIKV) Replication in HeLa Cells by Altering Viral Infectivity |
| title_fullStr | Favipiravir Inhibits Zika Virus (ZIKV) Replication in HeLa Cells by Altering Viral Infectivity |
| title_full_unstemmed | Favipiravir Inhibits Zika Virus (ZIKV) Replication in HeLa Cells by Altering Viral Infectivity |
| title_short | Favipiravir Inhibits Zika Virus (ZIKV) Replication in HeLa Cells by Altering Viral Infectivity |
| title_sort | favipiravir inhibits zika virus zikv replication in hela cells by altering viral infectivity |
| topic | favipiravir Zika virus antiviral therapy infectivity |
| url | https://www.mdpi.com/2076-2607/11/5/1097 |
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