Fatty acid synthase and stearoyl-CoA desaturase-1 are conserved druggable cofactors of Old World Alphavirus genome replication

Bakhache, William; Neyret, Aymeric; McKellar, Joe; Clop, Camille; Bernard, Éric; Weger-Lucarelli, James; Briant, Laurence

doi:10.1016/j.antiviral.2019.104642

Cited by 22 publications

(22 citation statements)

References 58 publications

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“…Elongation of the phospholipid membranes can be aided by channeling fatty acid into phospholipid synthesis 28 . Modulation of fatty acid metabolism has been shown to impact several viruses such as dengue virus, hepatitis C virus, and Old World alphaviruses 18,29,30 . Two well-described compounds that inhibit fatty acid metabolism are Orlistat and Triacsin C, both of which have been shown to have antiviral activity 19,30 .…”

Section: Inhibition Of Fatty Acid Metabolism Inhibits Sars-cov-2 Replmentioning

confidence: 99%

Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication

Silvas

Jureka

Nicolini

et al. 2020

Preprint

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Therapeutics targeting replication of SARS coronavirus 2 (SARS-CoV-2) are urgently needed. Coronaviruses rely on host membranes for entry, establishment of replication centers and egress. Compounds targeting cellular membrane biology and lipid biosynthetic pathways have previously shown promise as antivirals and are actively being pursued as treatments for other conditions. Here, we tested small molecule inhibitors that target membrane dynamics or lipid metabolism. Included were inhibitors of the PI3 kinase VPS34, which functions in autophagy, endocytosis and other processes; Orlistat, an inhibitor of lipases and fatty acid synthetase, is approved by the FDA as a treatment for obesity; and Triacsin C which inhibits long chain fatty acyl-CoA synthetases. VPS34 inhibitors, Orlistat and Triacsin C inhibited virus growth in Vero E6 cells and in the human airway epithelial cell line Calu-3, acting at a post-entry step in the virus replication cycle. Of these the VPS34 inhibitors exhibit the most potent activity.

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Section: Inhibition Of Fatty Acid Metabolism Inhibits Sars-cov-2 Replmentioning

confidence: 99%

Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication

Silvas

Jureka

Nicolini

et al. 2020

Preprint

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“…Upon enterovirus A71 and coxsackievirus A16 infection, disturbed lipid homeostasis in the infected cells has been shown to be related to virus replication ( Yan et al, 2019b ). Fatty acid synthase and stearoyl-CoA desaturase required for fatty acid metabolism have been demonstrated to be required for chikungunya virus infection ( Bakhache et al, 2019 ). Cholesterol can also affect hemagglutinin fusion activity and hence the virus assembly of influenza virus ( Hu et al, 2019b ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the lipidomic profile of BmN cells in response to Bombyx mori cytoplasmic polyhedrosis virus infection

Zhang

Shi

et al. 2021

Developmental & Comparative Immunology

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Bombyx mori cytoplasmic polyhedrosis virus (BmCPV)that belongs to the genus Cypovirus in the family of Reoviridae is one of the problematic pathogens in sericulture. In our previous study, we have found that lipid-related constituents in the host cellular membrane are associated with the BmCPV life cycle. It is important to note that the lipids not only affect the cellular biological processes, they also impact the virus life cycle. However, the intracellular lipid homeostasis in BmN cells after BmCPV infection remains unclear. Here, the lipid metabolism in BmCPV-infected BmN cells was studied by lipidomics analysis. Our results revealed that the intracellular lipid homeostasis was disturbed in BmN cells upon BmCPV infection. Major lipids constituents in cellular membrane were found to be significantly induced upon BmCPV infection, which included triglycerides, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, phospholipids, glucoside ceramide, monoetherphosphatidylcholin, ceramide, ceramide phosphoethanolamine and cardiolipin. Further analysis of the pathways related to these altered lipids (such as PE and PC) showed that glycerophospholipid metabolism was one of the most enriched pathways. These results suggested that BmCPV may manipulate the lipid metabolism of cells for their own interest. The findings may facilitate a better understanding of the roles of lipid metabolic changes during virus infection in future studies.

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Section: Antiviral Strategiesmentioning

confidence: 99%

“…The fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD1) are two key enzymes which are essential for the de novo synthesis of long-chain fatty acids and their early desaturation, respectively [ 54 ]. Both enzymes were shown to play an important role during the replication of arthritogenic alphaviruses such as CHIKV and MAYV [ 54 , 55 ]. Inhibition of FASN activity (by the anti-obesity drug orlistat ( Figure 3 ) [ 54 , 55 ] or the antibiotic cerulenin [ 54 ]), as well as the SCD1 activity (by CAY10566) [ 54 ], reduced the in vitro replication of both CHIKV and MAYV.…”

Section: Antiviral Strategiesmentioning

confidence: 99%

“…Both enzymes were shown to play an important role during the replication of arthritogenic alphaviruses such as CHIKV and MAYV [ 54 , 55 ]. Inhibition of FASN activity (by the anti-obesity drug orlistat ( Figure 3 ) [ 54 , 55 ] or the antibiotic cerulenin [ 54 ]), as well as the SCD1 activity (by CAY10566) [ 54 ], reduced the in vitro replication of both CHIKV and MAYV. Interference of the cellular cholesterol trafficking by the antidepressant drug imipramine ( Figure 3 ) reduced CHIKV replication in human skin fibroblasts in a dose-dependent manner [ 56 ].…”

Section: Antiviral Strategiesmentioning

confidence: 99%

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Antiviral Strategies against Arthritogenic Alphaviruses

Abdelnabi

2020

Microorganisms

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Alphaviruses are members of the Togaviridae family that are mainly transmitted by arthropods such as mosquitoes. In the last decades, several alphaviruses have re-emerged, causing outbreaks worldwide. One example is the re-emergence of chikungunya virus (CHIKV) in 2004, which caused massive epidemics in the Indian Ocean region after which the virus dramatically spread to the Americas in late 2013. Besides CHIKV, other alphaviruses, such as the Ross River virus (RRV), Mayaro virus (MAYV), and Venezuelan equine encephalitis virus (VEEV), have emerged and have become a serious public health concern in recent years. Infections with the Old World alphaviruses (e.g., CHIKV, RRV) are primarily associated with polyarthritis and myalgia that can persist for months to years. On the other hand, New World alphaviruses such as VEEV cause mainly neurological disease. Despite the worldwide (re-)emergence of these viruses, there are no antivirals or vaccines available for the treatment or prevention of infections with alphaviruses. It is therefore of utmost importance to develop antiviral strategies against these viruses. We here provided an overview of the reported antiviral strategies against arthritogenic alphaviruses. In addition, we highlighted the future perspectives for the development and the proper use of such antivirals.

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Fatty acid synthase and stearoyl-CoA desaturase-1 are conserved druggable cofactors of Old World Alphavirus genome replication

Cited by 22 publications

References 58 publications

Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication

Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication

Characterization of the lipidomic profile of BmN cells in response to Bombyx mori cytoplasmic polyhedrosis virus infection

Antiviral Strategies against Arthritogenic Alphaviruses

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