Targeting host metabolism by inhibition of acetyl-Coenzyme A carboxylase reduces flavivirus infection in mouse models

References

• Simmonds P, Becher P, Bukh J, et al. ICTV virus Taxonomy Profile: Flaviviridae. J Gen Virol. 2017 Jan;98(1):2–3. PubMed PMID: 28218572; PubMed Central PMCID: PMC5370391. eng. doi: 10.1099/jgv.0.000672
   PubMed Web of Science ®Google Scholar
• Martin-Acebes MA, Saiz JC. West Nile virus: A re-emerging pathogen revisited. World J Virol. 2012 Apr 12;1(2):51–70. PubMed PMID: 24175211; PubMed Central PMCID: PMC3782267. Eng. doi: 10.5501/wjv.v1.i2.51
   PubMedGoogle Scholar
• Saiz JC, Vazquez-Calvo A, Blazquez AB, et al. Zika virus: the Latest Newcomer. Front Microbiol. 2016;7(496). PubMed PMID: 27148186; PubMed Central PMCID: PMC4835484. eng. doi: 10.3389/fmicb.2016.00496
   Web of Science ®Google Scholar
• Guzman MG, Dengue HE. Dengue. Lancet. 2015 Jan 31;385(9966):453–465. PubMed PMID: 25230594; eng. doi: 10.1016/S0140-6736(14)60572-9
   PubMed Web of Science ®Google Scholar
• Barzon L, Pacenti M, Palu G. West Nile virus and kidney disease. Expert Rev Anti Infect Ther. 2013 May;11(5):479–487. PubMed PMID: 23627854; eng. doi: 10.1586/eri.13.34
   PubMed Web of Science ®Google Scholar
• Kaufmann SHE, Dorhoi A, Hotchkiss RS, et al. Host-directed therapies for bacterial and viral infections. Nat Rev Drug Discov. 2018 Jan;17(1):35–56. PubMed PMID: 28935918; eng. doi: 10.1038/nrd.2017.162
   PubMed Web of Science ®Google Scholar
• Boldescu V, Behnam MAM, Vasilakis N, et al. Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond. Nat Rev Drug Discov. 2017 Aug;16(8):565–586. PubMed PMID: 28473729; PubMed Central PMCID: PMC5925760. eng. doi: 10.1038/nrd.2017.33
   PubMed Web of Science ®Google Scholar
• Krishnan MN, Garcia-Blanco MA. Targeting host factors to treat West Nile and dengue viral infections. Viruses. 2014 Feb 10;6(2):683–708. PubMed PMID: 24517970; PubMed Central PMCID: PMC3939478. eng. doi: 10.3390/v6020683
   PubMed Web of Science ®Google Scholar
• Saiz JC, Martin-Acebes MA. The Race To find antivirals for Zika virus. Antimicrob Agents Chemother. 2017 Jun;61(6). PubMed PMID: 28348160; PubMed Central PMCID: PMC5444186. eng. doi:10.1128/AAC.00411-17.
   Web of Science ®Google Scholar
• Munger J, Bennett BD, Parikh A, et al. Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy. Nat Biotechnol. 2008 Oct;26(10):1179–1186. PubMed PMID: 18820684; PubMed Central PMCID: PMC2825756. eng. doi: 10.1038/nbt.1500
   PubMed Web of Science ®Google Scholar
• Martin-Acebes MA, Vazquez-Calvo A, Saiz JC. Lipids and flaviviruses, present and future perspectives for the control of dengue, Zika, and West Nile viruses. Prog Lipid Res. 2016 Oct;64:123–137. PubMed PMID: 27702593; eng. doi: 10.1016/j.plipres.2016.09.005
   PubMed Web of Science ®Google Scholar
• Spencer CM, Schafer XL, Moorman NJ, et al. Human cytomegalovirus induces the activity and expression of acetyl-coenzyme A carboxylase, a fatty acid biosynthetic enzyme whose inhibition attenuates viral replication. J Virol. 2011 Jun;85(12):5814–5824. PubMed PMID: 21471234; PubMed Central PMCID: PMC3126312. eng. doi: 10.1128/JVI.02630-10
   PubMed Web of Science ®Google Scholar
• Greseth MD, Traktman P. De novo fatty acid biosynthesis contributes significantly to establishment of a bioenergetically favorable environment for vaccinia virus infection. PLoS Pathog. 2014 Mar;10(3):e1004021. PubMed PMID: 24651651; PubMed Central PMCID: PMC3961357. eng. doi: 10.1371/journal.ppat.1004021
   PubMed Web of Science ®Google Scholar
• Nchoutmboube JA, Viktorova EG, Scott AJ, et al. Increased long chain acyl-Coa synthetase activity and fatty acid import is linked to membrane synthesis for development of picornavirus replication organelles. PLoS Pathog. 2013;9(6):e1003401. PubMed PMID: 23762027; PubMed Central PMCID: PMC3675155. eng. doi: 10.1371/journal.ppat.1003401
   PubMed Web of Science ®Google Scholar
• Koutsoudakis G, Romero-Brey I, Berger C, et al. Soraphen A: A broad-spectrum antiviral natural product with potent anti-hepatitis C virus activity. J Hepatol. 2015 Oct;63(4):813–821. PubMed PMID: 26070407; eng. doi: 10.1016/j.jhep.2015.06.002
   PubMed Web of Science ®Google Scholar
• Lyn RK, Singaravelu R, Kargman S, et al. Stearoyl-CoA desaturase inhibition blocks formation of hepatitis C virus-induced specialized membranes. Sci Rep. 2014 Apr 1;4:4549. PubMed PMID: 25008545; PubMed Central PMCID: PMC4091094. eng. doi: 10.1038/srep04549
   PubMed Web of Science ®Google Scholar
• Fleta-Soriano E, Smutna K, Martinez JP, et al. The Myxobacterial Metabolite Soraphen A inhibits HIV-1 by Reducing virus production and Altering virion Composition. Antimicrob Agents Chemother. 2017 Aug;61(8). PubMed PMID: 28533249; PubMed Central PMCID: PMC5527598. eng. doi: 10.1128/AAC.00739-17
   PubMed Web of Science ®Google Scholar
• Heaton NS, Perera R, Berger KL, et al. Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis. Proc. Natl. Acad. Sci. U.S.A.. 2010 Oct 5;107(40):17345–17350. PubMed PMID: 20855599; PubMed Central PMCID: PMC2951450. eng. doi: 10.1073/pnas.1010811107
   PubMed Web of Science ®Google Scholar
• Heaton NS, Randall G. Dengue virus-induced autophagy regulates lipid metabolism. Cell Host Microbe. 2010 Nov 18;8(5):422–432. PubMed PMID: 21075353; PubMed Central PMCID: PMC3026642. eng. doi: 10.1016/j.chom.2010.10.006
   PubMed Web of Science ®Google Scholar
• Martin-Acebes MA, Blazquez AB, de Oya NJ, et al. West Nile virus replication requires fatty acid synthesis but is independent on phosphatidylinositol-4-phosphate lipids. PloS one. 2011;6(9):e24970. PubMed PMID: 21949814; PubMed Central PMCID: PMC3176790. eng. doi: 10.1371/journal.pone.0024970
   PubMed Web of Science ®Google Scholar
• Perera R, Riley C, Isaac G, et al. Dengue virus infection perturbs lipid homeostasis in infected mosquito cells. PLoS Pathog. 2012 Mar;8(3):e1002584. PubMed PMID: 22457619; PubMed Central PMCID: PMC3310792. eng. doi: 10.1371/journal.ppat.1002584
   PubMed Web of Science ®Google Scholar
• Merino-Ramos T, Vazquez-Calvo A, Casas J, et al. Modification of the host cell lipid metabolism induced by Hypolipidemic drugs targeting the acetyl Coenzyme A carboxylase impairs West Nile virus replication. Antimicrob Agents Chemother. 2015 Jan;60(1):307–315. PubMed PMID: 26503654; PubMed Central PMCID: PMC4704205. eng. doi: 10.1128/AAC.01578-15
   PubMed Web of Science ®Google Scholar
• Kao YT, Chang BL, Liang JJ, et al. Japanese encephalitis virus nonstructural protein NS5 interacts with mitochondrial trifunctional protein and impairs fatty acid beta-oxidation. PLoS Pathog. 2015 Mar;11(3):e1004750. PubMed PMID: 25816318; PubMed Central PMCID: PMC4376648. eng. doi: 10.1371/journal.ppat.1004750
   PubMed Web of Science ®Google Scholar
• Saggerson D. Malonyl-CoA, a key signaling molecule in mammalian cells. Annu Rev Nutr. 2008;28:253–272. PubMed PMID: 18598135; eng. doi: 10.1146/annurev.nutr.28.061807.155434
   PubMed Web of Science ®Google Scholar
• Tong L, Harwood HJ, Jr. Acetyl-coenzyme A carboxylases: versatile targets for drug discovery. J Cell Biochem. 2006 Dec 15;99(6):1476–1488. PubMed PMID: 16983687; PubMed Central PMCID: PMC3837461. eng. doi: 10.1002/jcb.21077
   PubMed Web of Science ®Google Scholar
• Jimenez de Oya N, Blazquez AB, Casas J, et al. Direct Activation of adenosine monophosphate-activated protein Kinase (AMPK) by PF-06409577 inhibits flavivirus infection through modification of host-cell lipid metabolism. Antimicrob Agents Chemother. 2018 Apr 30. PubMed PMID: 29712653; eng. doi:10.1128/AAC.00360-18.
   PubMed Web of Science ®Google Scholar
• Griffith DA, Kung DW, Esler WP, et al. Decreasing the rate of metabolic ketone reduction in the discovery of a clinical acetyl-CoA carboxylase inhibitor for the treatment of diabetes. J Med Chem. 2014 Dec 26;57(24):10512–10526. PubMed PMID: 25423286; PubMed Central PMCID: PMC4281100. eng. doi: 10.1021/jm5016022
   PubMed Web of Science ®Google Scholar
• Bagley SW, Griffith DA, Kung DW. inventors; Pfizer Inc., assignee. N1-pyrazolospiroketone acetyl-Coa carboxylase inhibitors. US 2011111046. May 2011.
   Google Scholar
• Dow LR, Edmonds DJ, Griffith DA, et al. inventors; Pfizer Inc., assignee. Substituted acetyl-CoA carboxylase inhibitors. US 2012270893. Oct 2012.
   Google Scholar
• Di L, Whitney-Pickett C, Umland JP, et al. Development of a new permeability assay using low-efflux MDCKII cells. J Pharm Sci. 2011 Nov;100(11):4974–4985. PubMed PMID: 21766308; eng. doi: 10.1002/jps.22674
   PubMed Web of Science ®Google Scholar
• Hoehn KL, Turner N, Swarbrick MM, et al. Acute or chronic upregulation of mitochondrial fatty acid oxidation has no net effect on whole-body energy expenditure or adiposity. Cell Metab. 2010 Jan;11(1):70–76. PubMed PMID: 20074529; PubMed Central PMCID: PMC2824926. eng. doi: 10.1016/j.cmet.2009.11.008
   PubMed Web of Science ®Google Scholar
• Martin-Acebes MA, Merino-Ramos T, Blazquez AB, et al. The composition of west Nile virus lipid envelope unveils a role of sphingolipid metabolism in flavivirus biogenesis. J Virol. 2014 Oct 15;88(20):12041–12054. PubMed PMID: 25122799; eng. doi: 10.1128/JVI.02061-14
   PubMed Web of Science ®Google Scholar
• Abu-Elheiga L, Matzuk MM, Kordari P, et al. Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal. Proc. Natl. Acad. Sci. U.S.A.. 2005 Aug 23;102(34):12011–12016. PubMed PMID: 16103361; PubMed Central PMCID: PMC1189351. eng. doi: 10.1073/pnas.0505714102
   PubMed Web of Science ®Google Scholar
• Vazquez-Calvo A, de Oya N J, Martin-Acebes MA, et al. Antiviral properties of the Natural Polyphenols Delphinidin and Epigallocatechin gallate against the flaviviruses West Nile virus, Zika virus, and dengue virus. Front Microbiol. 2017;8:1314. PubMed PMID: 28744282; PubMed Central PMCID: PMC5504193. eng. doi: 10.3389/fmicb.2017.01314
   PubMed Web of Science ®Google Scholar
• Merino-Ramos T, Blazquez AB, Escribano-Romero E, et al. Protection of a single dose West Nile virus Recombinant Subviral particle Vaccine against Lineage 1 or 2 Strains and analysis of the Cross-Reactivity with Usutu virus. PloS one. 2014;9(9):e108056. PubMed PMID: 25229345; Eng. doi: 10.1371/journal.pone.0108056
   PubMed Web of Science ®Google Scholar
• Apte-Sengupta S, Sirohi D, Kuhn RJ. Coupling of replication and assembly in flaviviruses. Curr Opin Virol. 2014 Dec;9:134–142. PubMed PMID: 25462445; PubMed Central PMCID: PMC4268268. eng. doi: 10.1016/j.coviro.2014.09.020
   PubMed Web of Science ®Google Scholar
• Villareal VA, Rodgers MA, Costello DA, et al. Targeting host lipid synthesis and metabolism to inhibit dengue and hepatitis C viruses. Antiviral Res. 2015 Dec;124:110–121. PubMed PMID: 26526588; PubMed Central PMCID: PMC4699661. eng. doi: 10.1016/j.antiviral.2015.10.013
   PubMed Web of Science ®Google Scholar
• Zhang J, Lan Y, Sanyal S. Modulation of lipid Droplet metabolism-A potential target for therapeutic intervention in Flaviviridae infections. Front Microbiol. 2017;8:2286. PubMed PMID: 29234310; PubMed Central PMCID: PMC5712332. eng. doi: 10.3389/fmicb.2017.02286
   PubMed Web of Science ®Google Scholar
• Pombo JP, Sanyal S. Perturbation of Intracellular cholesterol and fatty acid Homeostasis during flavivirus infections. Front Immunol. 2018;9:1276. PubMed PMID: 29915602; PubMed Central PMCID: PMC5994796. eng. doi: 10.3389/fimmu.2018.01276
   PubMed Web of Science ®Google Scholar
• Leier HC, Messer WB, Tafesse FG. Lipids and pathogenic flaviviruses: An intimate union. PLoS Pathog. 2018 May;14(5):e1006952. PubMed PMID: 29746606; PubMed Central PMCID: PMC5944919. eng. doi: 10.1371/journal.ppat.1006952
   PubMed Web of Science ®Google Scholar
• Martinez-Gutierrez M, Correa-Londono LA, Castellanos JE, et al. Lovastatin delays infection and increases survival rates in AG129 mice infected with dengue virus serotype 2. PloS one. 2014;9(2):e87412. PubMed PMID: 24586275; PubMed Central PMCID: PMC3931612. eng. doi: 10.1371/journal.pone.0087412
   PubMed Web of Science ®Google Scholar
• Li C, Deng YQ, Wang S, et al. 25-Hydroxycholesterol Protects host against Zika virus infection and Its associated microcephaly in a mouse model. Immunity. 2017 Mar 21;46(3):446–456. PubMed PMID: 28314593; PubMed Central PMCID: PMC5957489. eng. doi: 10.1016/j.immuni.2017.02.012
   PubMed Web of Science ®Google Scholar
• Martin-Acebes MA, Gabande-Rodriguez E, Garcia-Cabrero AM, et al. Host sphingomyelin increases West Nile virus infection in vivo. J Lipid Res. 2016 Mar;57(3):422–432. PubMed PMID: 26764042; PubMed Central PMCID: PMC4766991. eng. doi: 10.1194/jlr.M064212
   PubMed Web of Science ®Google Scholar
• Taniguchi M, Tasaki T, Ninomiya H, et al. Sphingomyelin generated by sphingomyelin synthase 1 is involved in attachment and infection with Japanese encephalitis virus. Sci Rep. 2016 Nov 28;6(37829). PubMed PMID: 27892528; PubMed Central PMCID: PMC5124946. eng. doi:10.1038/srep37829.
   Google Scholar
• Saxena V, Xie G, Li B, et al. A hamster-derived West Nile virus isolate induces persistent renal infection in mice. PLoS Negl Trop Dis. 2013;7(6):e2275. PubMed PMID: 23785537; PubMed Central PMCID: PMC3681636. eng. doi: 10.1371/journal.pntd.0002275
   PubMed Web of Science ®Google Scholar
• Barzon L, Pacenti M, Franchin E, et al. Excretion of West Nile virus in urine during acute infection. The Journal f Infectious Diseases. 2013 Oct 1;208(7):1086–1092. PubMed PMID: 23821721; eng. doi: 10.1093/infdis/jit290
   PubMed Web of Science ®Google Scholar
• Murray KO, Kolodziej S, Ronca SE, et al. Visualization of West Nile virus in urine Sediment using Electron Microscopy and Immunogold up to Nine years Postinfection. Am J Trop Med Hyg. 2017 Dec;97(6):1913–1919. PubMed PMID: 29141749; PubMed Central PMCID: PMC5805063. eng. doi: 10.4269/ajtmh.17-0405
   PubMed Web of Science ®Google Scholar
• Nolan MS, Podoll AS, Hause AM, et al. Prevalence of chronic kidney disease and progression of disease over time among patients enrolled in the Houston West Nile virus cohort. PloS one. 2012;7(7):e40374. PubMed PMID: 22792293; PubMed Central PMCID: PMC3391259. eng. doi: 10.1371/journal.pone.0040374
   PubMed Web of Science ®Google Scholar
• Ergunay K, Karagul A, Abudalal A, et al. Prospective investigation of the impact of West Nile virus infections in renal diseases. J Med Virol. 2015 Oct;87(10):1625–1632. PubMed PMID: 25965349; eng. doi: 10.1002/jmv.24226
   PubMed Web of Science ®Google Scholar
• Murray K, Walker C, Herrington E, et al. Persistent infection with West Nile virus years after initial infection. J Infect Dis. 2015 Jan 1;201(1):2–4. PubMed PMID: 19961306; PubMed Central PMCID: PMC2791189. eng. doi: 10.1086/648731
   Web of Science ®Google Scholar
• Opie LH. Present status of statin therapy. Trends Cardiovasc Med. 2015 Apr;25(3):216–225. PubMed PMID: 25802224; Eng. doi: 10.1016/j.tcm.2014.10.002
   PubMed Web of Science ®Google Scholar
• Hardie DG. Keeping the home fires burning: AMP-activated protein kinase. J R Soc Interface. 2018 Jan;15(138):20170774. PubMed PMID: 29343628; PubMed Central PMCID: PMC5805978. eng. doi: 10.1098/rsif.2017.0774
   PubMed Web of Science ®Google Scholar
• Jones JE, Esler WP, Patel R, et al. Inhibition of acetyl-CoA carboxylase 1 (ACC1) and 2 (ACC2) reduces Proliferation and De novo lipogenesis of EGFRvIII human Glioblastoma cells. PloS one. 2017;12(1):e0169566. PubMed PMID: 28081256; PubMed Central PMCID: PMC5231342 ONE policies on sharing data and materials. eng. doi: 10.1371/journal.pone.0169566
   PubMed Web of Science ®Google Scholar
• Aktepe TE, Pham H, Mackenzie JM. Differential utilisation of ceramide during replication of the flaviviruses West Nile and dengue virus. Virology. 2015 Jun 26;484:241–250. PubMed PMID: 26122470; Eng. doi: 10.1016/j.virol.2015.06.015
   PubMed Web of Science ®Google Scholar
• Liebscher S, Ambrose RL, Aktepe TE, et al. Phospholipase A2 activity during the replication cycle of the flavivirus West Nile virus. PLoS Pathog. 2018 Apr;14(4):e1007029. PubMed PMID: 29709018; PubMed Central PMCID: PMC5945048. eng. doi: 10.1371/journal.ppat.1007029
   PubMed Web of Science ®Google Scholar
• Jordan TX, Randall G. Dengue virus Activates the AMP Kinase-mTOR Axis To Stimulate a Proviral Lipophagy. J Virol. 2017 Jun 1;91(11). PubMed PMID: 28298606; PubMed Central PMCID: PMC5432877. eng. doi: 10.1128/JVI.02020-16
   Web of Science ®Google Scholar
• Zhang J, Lan Y, Li MY, et al. Flaviviruses Exploit the lipid Droplet protein AUP1 to Trigger Lipophagy and drive virus production. Cell Host Microbe. 2018 Jun 13;23(6):819–831 e5. PubMed PMID: 29902443; eng. doi: 10.1016/j.chom.2018.05.005
   PubMed Web of Science ®Google Scholar
• Aktepe TE, Mackenzie JM. Shaping the flavivirus replication complex: it's Curvaceous!. Cell Microbiol. 2018 Jun 22;20:e12884. PubMed PMID: 29933527; eng. doi: 10.1111/cmi.12884
   PubMed Web of Science ®Google Scholar