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Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2
SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in t...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883762/ https://www.ncbi.nlm.nih.gov/pubmed/35251918 http://dx.doi.org/10.1016/j.apsb.2022.02.019 |
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author | Aliyari, Saba R. Ghaffari, Amir Ali Pernet, Olivier Parvatiyar, Kislay Wang, Yao Gerami, Hoda Tong, Ann-Jay Vergnes, Laurent Takallou, Armin Zhang, Adel Wei, Xiaochao Chilin, Linda D. Wu, Yuntao Semenkovich, Clay F. Reue, Karen Smale, Stephen T. Lee, Benhur Cheng, Genhong |
author_facet | Aliyari, Saba R. Ghaffari, Amir Ali Pernet, Olivier Parvatiyar, Kislay Wang, Yao Gerami, Hoda Tong, Ann-Jay Vergnes, Laurent Takallou, Armin Zhang, Adel Wei, Xiaochao Chilin, Linda D. Wu, Yuntao Semenkovich, Clay F. Reue, Karen Smale, Stephen T. Lee, Benhur Cheng, Genhong |
author_sort | Aliyari, Saba R. |
collection | PubMed |
description | SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19. |
format | Online Article Text |
id | pubmed-8883762 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-88837622022-02-28 Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2 Aliyari, Saba R. Ghaffari, Amir Ali Pernet, Olivier Parvatiyar, Kislay Wang, Yao Gerami, Hoda Tong, Ann-Jay Vergnes, Laurent Takallou, Armin Zhang, Adel Wei, Xiaochao Chilin, Linda D. Wu, Yuntao Semenkovich, Clay F. Reue, Karen Smale, Stephen T. Lee, Benhur Cheng, Genhong Acta Pharm Sin B Original Article SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19. Elsevier 2022-04 2022-02-28 /pmc/articles/PMC8883762/ /pubmed/35251918 http://dx.doi.org/10.1016/j.apsb.2022.02.019 Text en © 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Aliyari, Saba R. Ghaffari, Amir Ali Pernet, Olivier Parvatiyar, Kislay Wang, Yao Gerami, Hoda Tong, Ann-Jay Vergnes, Laurent Takallou, Armin Zhang, Adel Wei, Xiaochao Chilin, Linda D. Wu, Yuntao Semenkovich, Clay F. Reue, Karen Smale, Stephen T. Lee, Benhur Cheng, Genhong Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2 |
title | Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2 |
title_full | Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2 |
title_fullStr | Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2 |
title_full_unstemmed | Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2 |
title_short | Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2 |
title_sort | suppressing fatty acid synthase by type i interferon and chemical inhibitors as a broad spectrum anti-viral strategy against sars-cov-2 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883762/ https://www.ncbi.nlm.nih.gov/pubmed/35251918 http://dx.doi.org/10.1016/j.apsb.2022.02.019 |
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