Favipiravir and ribavirin inhibit replication of Asian and African strains of zika virus in different cell models

Ji Ae Kim; Rak Kyun Seong; Mukesh Kumar; Ok Sarah Shin

doi:10.3390/v10020072

Favipiravir and ribavirin inhibit replication of Asian and African strains of zika virus in different cell models

Ji Ae Kim, Rak Kyun Seong, Mukesh Kumar, Ok Sarah Shin

Research output: Contribution to journal › Article › peer-review

60 Citations (Scopus)

Abstract

Zika virus (ZIKV) has recently emerged as a new public health threat. ZIKV infections have caused a wide spectrum of neurological diseases, such as Guillain–Barré syndrome, myelitis, meningoencephalitis, and congenital microcephaly. No effective therapies currently exist for treating patients infected with ZIKV. Herein, we evaluated the anti-viral activity of favipiravir (T-705) and ribavirin against Asian and African strains of ZIKV using different cell models, including human neuronal progenitor cells (hNPCs), human dermal fibroblasts (HDFs), human lung adenocarcinoma cells (A549) and Vero cells. Cells were treated with favipiravir or ribavirin and effects on ZIKV replication were determined using quantitative real-time PCR and plaque assay. Our results demonstrate that favipiravir or ribavirin treatment significantly inhibited ZIKV replication in a dose-dependent manner. Moreover, favipiravir treatment of ZIKV-infected hNPCs led to reduced cell death, enhanced AKT pathway phosphorylation, and increased expression of anti-apoptotic factor B cell lymphoma 2. In conclusion, our results demonstrate conclusively that favipiravir inhibits ZIKV replication and prevents cell death, and can be a promising intervention for ZIKV-associated disease.

Original language	English
Article number	72
Journal	Viruses
Volume	10
Issue number	2
DOIs	https://doi.org/10.3390/v10020072
Publication status	Published - 2018 Feb 9
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgments: We would like to thank Ho-Seok Song (Korea University School of Medicine) for providing hNPC and Vincent Racaneillo (Columbia University, New York, NY, USA) for providing the ZIKV plaque assay protocol. This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF), Ministry of Science, ICT & Future Planning (NRF-2016R1C1B2006493). M.K. is supported by a grant (P30GM114737) from the Centers of Biomedical Research Excellence, National Institute of General Medical Sciences, grant (R21NS099838) from National Institute of Neurological Disorders and Stroke, and grant (R21OD024896) from the Office of the Director, National Institutes of Health.

Funding Information:
We would like to thank Ho-Seok Song (Korea University School of Medicine) for providing hNPC and Vincent Racaneillo (Columbia University, New York, NY, USA) for providing the ZIKV plaque assay protocol. This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF), Ministry of Science, ICT & Future Planning (NRF-2016R1C1B2006493). M.K. is supported by a grant (P30GM114737) from the Centers of Biomedical Research Excellence, National Institute of General Medical Sciences, grant (R21NS099838) from National Institute of Neurological Disorders and Stroke, and grant (R21OD024896) from the Office of the Director, National Institutes of Health.

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Anti-viral
Favipiravir
HNPCs
Ribavirin
Zika virus

ASJC Scopus subject areas

Infectious Diseases
Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/v10020072

Cite this

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title = "Favipiravir and ribavirin inhibit replication of Asian and African strains of zika virus in different cell models",

abstract = "Zika virus (ZIKV) has recently emerged as a new public health threat. ZIKV infections have caused a wide spectrum of neurological diseases, such as Guillain–Barr{\'e} syndrome, myelitis, meningoencephalitis, and congenital microcephaly. No effective therapies currently exist for treating patients infected with ZIKV. Herein, we evaluated the anti-viral activity of favipiravir (T-705) and ribavirin against Asian and African strains of ZIKV using different cell models, including human neuronal progenitor cells (hNPCs), human dermal fibroblasts (HDFs), human lung adenocarcinoma cells (A549) and Vero cells. Cells were treated with favipiravir or ribavirin and effects on ZIKV replication were determined using quantitative real-time PCR and plaque assay. Our results demonstrate that favipiravir or ribavirin treatment significantly inhibited ZIKV replication in a dose-dependent manner. Moreover, favipiravir treatment of ZIKV-infected hNPCs led to reduced cell death, enhanced AKT pathway phosphorylation, and increased expression of anti-apoptotic factor B cell lymphoma 2. In conclusion, our results demonstrate conclusively that favipiravir inhibits ZIKV replication and prevents cell death, and can be a promising intervention for ZIKV-associated disease.",

keywords = "Anti-viral, Favipiravir, HNPCs, Ribavirin, Zika virus",

author = "Kim, {Ji Ae} and Seong, {Rak Kyun} and Mukesh Kumar and Shin, {Ok Sarah}",

note = "Funding Information: Acknowledgments: We would like to thank Ho-Seok Song (Korea University School of Medicine) for providing hNPC and Vincent Racaneillo (Columbia University, New York, NY, USA) for providing the ZIKV plaque assay protocol. This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF), Ministry of Science, ICT & Future Planning (NRF-2016R1C1B2006493). M.K. is supported by a grant (P30GM114737) from the Centers of Biomedical Research Excellence, National Institute of General Medical Sciences, grant (R21NS099838) from National Institute of Neurological Disorders and Stroke, and grant (R21OD024896) from the Office of the Director, National Institutes of Health. Funding Information: We would like to thank Ho-Seok Song (Korea University School of Medicine) for providing hNPC and Vincent Racaneillo (Columbia University, New York, NY, USA) for providing the ZIKV plaque assay protocol. This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF), Ministry of Science, ICT & Future Planning (NRF-2016R1C1B2006493). M.K. is supported by a grant (P30GM114737) from the Centers of Biomedical Research Excellence, National Institute of General Medical Sciences, grant (R21NS099838) from National Institute of Neurological Disorders and Stroke, and grant (R21OD024896) from the Office of the Director, National Institutes of Health. Publisher Copyright: {\textcopyright} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Kim, Ji Ae

AU - Seong, Rak Kyun

AU - Kumar, Mukesh

AU - Shin, Ok Sarah

N1 - Funding Information: Acknowledgments: We would like to thank Ho-Seok Song (Korea University School of Medicine) for providing hNPC and Vincent Racaneillo (Columbia University, New York, NY, USA) for providing the ZIKV plaque assay protocol. This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF), Ministry of Science, ICT & Future Planning (NRF-2016R1C1B2006493). M.K. is supported by a grant (P30GM114737) from the Centers of Biomedical Research Excellence, National Institute of General Medical Sciences, grant (R21NS099838) from National Institute of Neurological Disorders and Stroke, and grant (R21OD024896) from the Office of the Director, National Institutes of Health. Funding Information: We would like to thank Ho-Seok Song (Korea University School of Medicine) for providing hNPC and Vincent Racaneillo (Columbia University, New York, NY, USA) for providing the ZIKV plaque assay protocol. This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF), Ministry of Science, ICT & Future Planning (NRF-2016R1C1B2006493). M.K. is supported by a grant (P30GM114737) from the Centers of Biomedical Research Excellence, National Institute of General Medical Sciences, grant (R21NS099838) from National Institute of Neurological Disorders and Stroke, and grant (R21OD024896) from the Office of the Director, National Institutes of Health. Publisher Copyright: © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

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N2 - Zika virus (ZIKV) has recently emerged as a new public health threat. ZIKV infections have caused a wide spectrum of neurological diseases, such as Guillain–Barré syndrome, myelitis, meningoencephalitis, and congenital microcephaly. No effective therapies currently exist for treating patients infected with ZIKV. Herein, we evaluated the anti-viral activity of favipiravir (T-705) and ribavirin against Asian and African strains of ZIKV using different cell models, including human neuronal progenitor cells (hNPCs), human dermal fibroblasts (HDFs), human lung adenocarcinoma cells (A549) and Vero cells. Cells were treated with favipiravir or ribavirin and effects on ZIKV replication were determined using quantitative real-time PCR and plaque assay. Our results demonstrate that favipiravir or ribavirin treatment significantly inhibited ZIKV replication in a dose-dependent manner. Moreover, favipiravir treatment of ZIKV-infected hNPCs led to reduced cell death, enhanced AKT pathway phosphorylation, and increased expression of anti-apoptotic factor B cell lymphoma 2. In conclusion, our results demonstrate conclusively that favipiravir inhibits ZIKV replication and prevents cell death, and can be a promising intervention for ZIKV-associated disease.

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KW - Ribavirin

KW - Zika virus

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Favipiravir and ribavirin inhibit replication of Asian and African strains of zika virus in different cell models

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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