Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2.
Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2.
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DOI：
10.1016/j.apsb.2022.02.019
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Cheng G
中科院分区：
文献类型：
--
作者：
Aliyari SR;Ghaffari AA;Pernet O;Parvatiyar K;Wang Y;Gerami H;Tong AJ;Vergnes L;Takallou A;Zhang A;Wei X;Chilin LD;Wu Y;Semenkovich CF;Reue K;Smale ST;Lee B;Cheng G
SARS-CoV-2是一种新出现的病毒病原体，自2019年12月以来一直是全球公共卫生的重大挑战，在整个大流行期间有效治疗有限。作为对病毒感染的先天性免疫反应的一部分，I型干扰素(IFN-I)触发了一系列信号级联，最终激活了数百个基因，即干扰素刺激基因(ISGs)，这些基因共同促进了抗病毒状态。我们在此报告了一组I型干扰素抑制基因的鉴定，包括脂肪酸合成酶(FASN)，它们参与了脂质代谢。FASN的过表达或其下游产物棕榈酸酯的添加增加了病毒感染，而FASN的敲除或敲除则减少了感染。更重要的是，FASN的药理抑制剂有效地阻止了多种病毒的感染，包括SARS-CoV-2及其令人担忧的变种。因此，我们的研究不仅表明，代谢基因的下调可能是I型干扰素的一种抗病毒策略，而且它们还引入了FASN抑制剂在对抗新冠肺炎等新出现的传染病方面具有治疗应用的潜力。I型干扰素介导的脂肪酸合成酶(FASN)下调导致病毒感染减少。FASN的药理抑制剂可能是一种新型的抗病毒药物，可以对抗包括SARS-CoV-2在内的包膜病毒。
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. Type I interferon-mediated downregulation of fatty acid synthase (FASN) results in decreased viral infection. Pharmacological inhibitors of FASN could be a novel antiviral therapy against enveloped viruses including SARS-CoV-2.
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DOI：
10.1002/art.41616
发表时间：
2021-04
期刊：
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