Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2

Saba R. Aliyari; Amir Ali Ghaffari; Olivier Pernet; Kislay Parvatiyar; Yao Wang; Hoda Gerami; Ann-Jay Tong; Laurent Vergnes; Armin Takallou; Adel Zhang; Xiaochao Wei; Linda D. Chilin; Yuntao Wu; Clay F. Semenkovich; Karen Reue; Stephen T. Smale; Benhur Lee; Genhong Cheng

Acta Pharmaceutica Sinica B (Apr 2022)

Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2

Saba R. Aliyari,
Amir Ali Ghaffari,
Olivier Pernet,
Kislay Parvatiyar,
Yao Wang,
Hoda Gerami,
Ann-Jay Tong,
Laurent Vergnes,
Armin Takallou,
Adel Zhang,
Xiaochao Wei,
Linda D. Chilin,
Yuntao Wu,
Clay F. Semenkovich,
Karen Reue,
Stephen T. Smale,
Benhur Lee,
Genhong Cheng

Affiliations

Saba R. Aliyari: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Amir Ali Ghaffari: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Olivier Pernet: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; EnViro International Laboratories, Los Angeles, CA 90077, USA
Kislay Parvatiyar: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Yao Wang: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Hoda Gerami: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Ann-Jay Tong: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Laurent Vergnes: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
Armin Takallou: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Adel Zhang: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Xiaochao Wei: Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, USA
Linda D. Chilin: Center for Infectious Disease Research, School of Systems Biology, George Mason University Manassas, VA 20110, USA
Yuntao Wu: Center for Infectious Disease Research, School of Systems Biology, George Mason University Manassas, VA 20110, USA
Clay F. Semenkovich: Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, USA; Diabetic Cardiovascular Disease Center, Washington, University School of Medicine, St. Louis, MO 63110, USA
Karen Reue: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
Stephen T. Smale: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Benhur Lee: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Genhong Cheng: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; Corresponding author. Tel.:+1 310 825 8896; fax: +1 310 206 5553.

Journal volume & issue: Vol. 12, no. 4
pp. 1624 – 1635

Abstract

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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.

Published in Acta Pharmaceutica Sinica B

ISSN: 2211-3835 (Print); 2211-3843 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/acta-pharmaceutica-sinica-b

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