Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other Flaviviruses
The Zika virus (ZIKV) is a mosquito-borne flavivirus that can lead to birth defects (microcephaly), ocular lesions and neurological disorders (Guillain-Barré syndrome). There is no licensed vaccine or antiviral treatment against ZIKV infection. The effort to understand the complex interacti...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-06-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/12/2/97 |
| _version_ | 1811285312622559232 |
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| author | Miguel A. Martín-Acebes Nereida Jiménez de Oya Juan-Carlos Saiz |
| author_facet | Miguel A. Martín-Acebes Nereida Jiménez de Oya Juan-Carlos Saiz |
| author_sort | Miguel A. Martín-Acebes |
| collection | DOAJ |
| description | The Zika virus (ZIKV) is a mosquito-borne flavivirus that can lead to birth defects (microcephaly), ocular lesions and neurological disorders (Guillain-Barré syndrome). There is no licensed vaccine or antiviral treatment against ZIKV infection. The effort to understand the complex interactions of ZIKV with cellular networks contributes to the identification of novel host-directed antiviral (HDA) candidates. Among the cellular pathways involved in infection, lipid metabolism gains attention. In ZIKV-infected cells lipid metabolism attributed to intracellular membrane remodeling, virion morphogenesis, autophagy modulation, innate immunity and inflammation. The key roles played by the cellular structures associated with lipid metabolism, such as peroxisomes and lipid droplets, are starting to be deciphered. Consequently, there is a wide variety of lipid-related antiviral strategies that are currently under consideration, which include an inhibition of sterol regulatory element-binding proteins (SREBP), the activation of adenosine-monophosphate activated kinase (AMPK), an inhibition of acetyl-Coenzyme A carboxylase (ACC), interference with sphingolipid metabolism, blockage of intracellular cholesterol trafficking, or a treatment with cholesterol derivatives. Remarkably, most of the HDAs identified in these studies are also effective against flaviviruses other than ZIKV (West Nile virus and dengue virus), supporting their broad-spectrum effect. Considering that lipid metabolism is one of the main cellular pathways suitable for pharmacological intervention, the idea of repositioning drugs targeting lipid metabolism as antiviral candidates is gaining force. |
| first_indexed | 2024-04-13T02:42:07Z |
| format | Article |
| id | doaj.art-7aaf5ca9f98c41239cb98115ab91cb52 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-04-13T02:42:07Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-7aaf5ca9f98c41239cb98115ab91cb522022-12-22T03:06:09ZengMDPI AGPharmaceuticals1424-82472019-06-011229710.3390/ph12020097ph12020097Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other FlavivirusesMiguel A. Martín-Acebes0Nereida Jiménez de Oya1Juan-Carlos Saiz2Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040 Madrid, SpainDepartment of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040 Madrid, SpainDepartment of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040 Madrid, SpainThe Zika virus (ZIKV) is a mosquito-borne flavivirus that can lead to birth defects (microcephaly), ocular lesions and neurological disorders (Guillain-Barré syndrome). There is no licensed vaccine or antiviral treatment against ZIKV infection. The effort to understand the complex interactions of ZIKV with cellular networks contributes to the identification of novel host-directed antiviral (HDA) candidates. Among the cellular pathways involved in infection, lipid metabolism gains attention. In ZIKV-infected cells lipid metabolism attributed to intracellular membrane remodeling, virion morphogenesis, autophagy modulation, innate immunity and inflammation. The key roles played by the cellular structures associated with lipid metabolism, such as peroxisomes and lipid droplets, are starting to be deciphered. Consequently, there is a wide variety of lipid-related antiviral strategies that are currently under consideration, which include an inhibition of sterol regulatory element-binding proteins (SREBP), the activation of adenosine-monophosphate activated kinase (AMPK), an inhibition of acetyl-Coenzyme A carboxylase (ACC), interference with sphingolipid metabolism, blockage of intracellular cholesterol trafficking, or a treatment with cholesterol derivatives. Remarkably, most of the HDAs identified in these studies are also effective against flaviviruses other than ZIKV (West Nile virus and dengue virus), supporting their broad-spectrum effect. Considering that lipid metabolism is one of the main cellular pathways suitable for pharmacological intervention, the idea of repositioning drugs targeting lipid metabolism as antiviral candidates is gaining force.https://www.mdpi.com/1424-8247/12/2/97Zika virusWest Nile virusdengue virusflavivirusantivirallipids |
| spellingShingle | Miguel A. Martín-Acebes Nereida Jiménez de Oya Juan-Carlos Saiz Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other Flaviviruses Pharmaceuticals Zika virus West Nile virus dengue virus flavivirus antiviral lipids |
| title | Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other Flaviviruses |
| title_full | Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other Flaviviruses |
| title_fullStr | Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other Flaviviruses |
| title_full_unstemmed | Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other Flaviviruses |
| title_short | Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other Flaviviruses |
| title_sort | lipid metabolism as a source of druggable targets for antiviral discovery against zika and other flaviviruses |
| topic | Zika virus West Nile virus dengue virus flavivirus antiviral lipids |
| url | https://www.mdpi.com/1424-8247/12/2/97 |
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