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

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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.

Author: Saba R ALIYARI ¹ ; Amir Ali GHAFFARI ¹ ; Olivier PERNET ¹ ; Kislay PARVATIYAR ¹ ; Yao WANG ¹ ; Hoda GERAMI ¹ ; Ann-Jay TONG ¹ ; Laurent VERGNES ² ; Armin TAKALLOU ¹ ; Adel ZHANG ¹ ; Xiaochao WEI ³ ; Linda D CHILIN ⁴ ; Yuntao WU ⁴ ; Clay F SEMENKOVICH ³ ; Karen REUE ² ; Stephen T SMALE ¹ ; Benhur LEE ¹ ; Genhong CHENG ¹
Author Information

1. Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
2. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
3. Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
4. Center for Infectious Disease Research, School of Systems Biology, George Mason University Manassas, VA 20110, USA.
Publication Type:Journal Article
Keywords: C75; COVID-19; Cerulenin; FASN; Fatty acid synthase; IFN-I; SARS-CoV-2; TVB-3166
From: Acta Pharmaceutica Sinica B 2022;12(4):1624-1635
CountryChina
Language:English
Abstract: 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.