@article{5a1f46a4b44444398531a21d3d0dde52,
title = "Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2",
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.",
keywords = "C75, COVID-19, Cerulenin, FASN, Fatty acid synthase, IFN-I, SARS-CoV-2, TVB-3166",
author = "Aliyari, {Saba R.} and Ghaffari, {Amir Ali} and Olivier Pernet and Kislay Parvatiyar and Yao Wang and Hoda Gerami and Tong, {Ann Jay} and Laurent Vergnes and Armin Takallou and Adel Zhang and Xiaochao Wei and Chilin, {Linda D.} and Yuntao Wu and Semenkovich, {Clay F.} and Karen Reue and Smale, {Stephen T.} and Benhur Lee and Genhong Cheng",
note = "Funding Information: This project is supported by the Research Funds from US National Institute of Health funds ( AI069120 , AI158154 , and AI149718 ), the UCLA AIDS Institute and UCLA David Geffen School of Medicine—Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Award Program and Tumor Immunology Training Grant ( T32CA912036A1 , USA). We thank Dr. Vaithilingarajai Arumugaswami at UCLA for sharing the SARS-CoV-2 variants of concerns obtained from the BEI resources. We thank Ms. Barbara Dillon, the director of the UCLA BSL3 facility for providing a safe and organized laboratory for performing the SARS-CoV-2-based research projects. Funding Information: This project is supported by the Research Funds from US National Institute of Health funds (AI069120, AI158154, and AI149718), the UCLA AIDS Institute and UCLA David Geffen School of Medicine—Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Award Program and Tumor Immunology Training Grant (T32CA912036A1, USA). We thank Dr. Vaithilingarajai Arumugaswami at UCLA for sharing the SARS-CoV-2 variants of concerns obtained from the BEI resources. We thank Ms. Barbara Dillon, the director of the UCLA BSL3 facility for providing a safe and organized laboratory for performing the SARS-CoV-2-based research projects. Publisher Copyright: {\textcopyright} 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences",
year = "2022",
month = apr,
doi = "10.1016/j.apsb.2022.02.019",
language = "English",
volume = "12",
pages = "1624--1635",
journal = "Acta Pharmaceutica Sinica B",
issn = "2211-3835",
number = "4",
}