Cerulenin inhibits production of mature virion particles in chick embryo fibroblasts infected by influenza A viruses

Conti, Stefania; Portincasa, P.; Chezzi, Carlo

doi:10.1016/0923-2516(96)81083-1

Cited by 6 publications

(4 citation statements)

References 20 publications

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“…Possibilities include precluding changes in membrane composition required for viral budding, impairing synthesis of specialized envelope phospholipids43, or impeding fatty acid modification of proteins44. Notably, hemagglutinin release from influenza A–infected cells is sensitive to the nonspecific lipid synthesis inhibitor cerulenin45. Similarly, hepatitis C virus replication is linked to host cholesterol synthesis through levels of geranylgeranyl pyrophosphate and activities of proteins found in cholesterol-rich membrane domains46.…”

Section: Discussionmentioning

confidence: 99%

Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy

et al. 2008

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Viruses rely on the metabolic network of their cellular hosts to provide energy and building blocks for viral replication. We developed a flux measurement approach based on liquid chromatography-tandem mass spectrometry to quantify changes in metabolic activity induced by human cytomegalovirus (HCMV). This approach reliably elucidated fluxes in cultured mammalian cells by monitoring metabolome labeling kinetics after feeding cells 13 C-labeled forms of glucose and glutamine. Infection with HCMV markedly upregulated flux through much of the central carbon metabolism, including glycolysis. Particularly notable increases occurred in flux through the tricarboxylic acid cycle and its efflux to the fatty acid biosynthesis pathway. Pharmacological inhibition of fatty acid biosynthesis suppressed the replication of both HCMV and influenza A, another enveloped virus. These results show that fatty acid synthesis is essential for the replication of two divergent enveloped viruses and that systems-level metabolic flux profiling can identify metabolic targets for antiviral therapy.The capability of mass spectrometry and nuclear magnetic resonance spectroscopy to quantify numerous metabolites simultaneously has given rise to the systems-level examination of metabolites (metabolomics) and their fluxes (fluxomics) [1][2][3] . Initial efforts to apply metabolomics to investigate human disease have focused largely on analysis of biofluids in normal versus affected individuals 4-7 . Although promising, such analysis is complicated by variation between individuals 8 . Moreover, the complexity of metabolic

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Section: Discussionmentioning

confidence: 99%

Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy

et al. 2008

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“…Interestingly, a specific FAS inhibitor, C75, preferentially inhibits the growth of tumor cells versus primary cells (30,42), suggesting that FAS activity may be important for the growth of certain tumors. In addition, the FAS inhibitor cerulenin inhibits the replication of several different viruses, including varicella-zoster virus, al-though the exact mechanisms for these effects have not been well defined (9,23,38).…”

mentioning

confidence: 99%

Fatty Acid Synthase Expression Is Induced by the Epstein-Barr Virus Immediate-Early Protein BRLF1 and Is Required for Lytic Viral Gene Expression

Li¹,

Webster‐Cyriaque

Tomlinson³

et al. 2004

J Virol

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“…Of note, cerulenin, gallium nitrate and orlistat are highly connected drugs that show interactions with six other pathogen types besides IAV, which imply repositioning potential for developing broad-spectrum antimicrobials. Through literature investigation, we found experimental evidence that supports the antiviral activity of cerulenin against IAV ( 21 ), HIV-1 ( 22 ) and West Nile virus ( 23 ). We also found gallium nitrate is bactericidal to M. fortuitum ( 24 , 25 ), which shares EHF with IAV.…”

Section: Application Case Studymentioning

confidence: 89%

EHFPI: a database and analysis resource of essential host factors for pathogenic infection

Liu¹,

Xie²,

Han³

et al. 2014

Nucleic Acids Research

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High-throughput screening and computational technology has greatly changed the face of microbiology in better understanding pathogen–host interactions. Genome-wide RNA interference (RNAi) screens have given rise to a new class of host genes designated as Essential Host Factors (EHFs), whose knockdown effects significantly influence pathogenic infections. Therefore, we present the first release of a manually-curated bioinformatics database and analysis resource EHFPI (Essential Host Factors for Pathogenic Infection, http://biotech.bmi.ac.cn/ehfpi). EHFPI captures detailed article, screen, pathogen and phenotype annotation information for a total of 4634 EHF genes of 25 clinically important pathogenic species. Notably, EHFPI also provides six powerful and data-integrative analysis tools, i.e. EHF Overlap Analysis, EHF-pathogen Network Analysis, Gene Enrichment Analysis, Pathogen Interacting Proteins (PIPs) Analysis, Drug Target Analysis and GWAS Candidate Gene Analysis, which advance the comprehensive understanding of the biological roles of EHF genes, as in diverse perspectives of protein–protein interaction network, drug targets and diseases/traits. The EHFPI web interface provides appropriate tools that allow efficient query of EHF data and visualization of custom-made analysis results. EHFPI data and tools shall keep available without charge and serve the microbiology, biomedicine and pharmaceutics research communities, to finally facilitate the development of diagnostics, prophylactics and therapeutics for human pathogens.

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Cerulenin inhibits production of mature virion particles in chick embryo fibroblasts infected by influenza A viruses

Cited by 6 publications

References 20 publications

Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy

Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy

Fatty Acid Synthase Expression Is Induced by the Epstein-Barr Virus Immediate-Early Protein BRLF1 and Is Required for Lytic Viral Gene Expression

EHFPI: a database and analysis resource of essential host factors for pathogenic infection

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