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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
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.
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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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