{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:43:38Z","timestamp":1792791818795,"version":"4.5.0"},"reference-count":81,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIAID","award":["1R16AI189452-01"],"award-info":[{"award-number":["1R16AI189452-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>5\u2032-Adenosine monophosphate-activated protein kinase (AMPK) is the principal cellular energy sensor that coordinates metabolic adaptation by balancing anabolic and catabolic pathways in response to energic stress. Beyond its canonical role in maintaining energy homeostasis, AMPK has emerged as a central regulator of host\u2013pathogen interactions by integrating lipid metabolism, autophagy, mitochondrial dynamics, oxidative stress, and innate immune signaling. Flaviviruses, including dengue virus, Zika virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus, extensively remodel host metabolism to establish productive infection. As a master regulator of cellular metabolism, AMPK can either restrict or facilitate flavivirus replication in a context-dependent manner by regulating lipid droplet biogenesis, fatty acid synthesis and beta-oxidation, autophagy, mitochondrial homeostasis, and interferon-mediated antiviral responses. Conversely, flaviviruses actively manipulate AMPK signaling and its downstream metabolic networks to promote endoplasmic reticulum remodeling, replication organelle biogenesis, energy production, and immune evasion. In this review, we summarize recent advances in understanding the multifaceted roles of AMPK during flavivirus infection, with an emphasis on its regulation of metabolic reprogramming, organelle remodeling, and antiviral immunity. We further discuss the therapeutic potential of pharmacologically targeting AMPK and its downstream pathways as a host-directed strategy for broad-spectrum antiviral intervention against flaviviruses.<\/jats:p>","DOI":"10.3390\/v18080910","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T09:30:53Z","timestamp":1787131853000},"page":"910","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["AMPK-Orchestrated Metabolic Reprogramming in Some Flavivirus Infections: Mechanisms and Therapeutic Opportunities"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3038-3676","authenticated-orcid":false,"given":"Kaci","family":"Craft","sequence":"first","affiliation":[{"name":"Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imaan","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1390-1801","authenticated-orcid":false,"given":"Shaokai","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6487-2356","authenticated-orcid":false,"given":"Qiyi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.coviro.2016.05.007","article-title":"Flavivirus modulation of cellular metabolism","volume":"19","author":"Jordan","year":"2016","journal-title":"Curr. Opin. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrm3311","article-title":"AMPK: A nutrient and energy sensor that maintains energy homeostasis","volume":"13","author":"Hardie","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Yan, Y., Zhou, X.E., Xu, H.E., and Melcher, K. (2018). Structure and Physiological Regulation of AMPK. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113534"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2477647","DOI":"10.1080\/22221751.2025.2477647","article-title":"Dengue virus and lipid metabolism: Unravelling the interplay for future therapeutic approaches","volume":"14","author":"Xie","year":"2025","journal-title":"Emerg. Microbes Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1074\/jbc.M116.763268","article-title":"AMP-activated Kinase (AMPK) Promotes Innate Immunity and Antiviral Defense through Modulation of Stimulator of Interferon Genes (STING) Signaling","volume":"292","author":"Prantner","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.str.2011.01.018","article-title":"Structural insights into the architecture and allostery of full-length AMP-activated protein kinase","volume":"19","author":"Zhu","year":"2011","journal-title":"Structure"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1080\/15548627.2023.2247300","article-title":"Interplay of energy metabolism and autophagy","volume":"20","author":"Feng","year":"2024","journal-title":"Autophagy"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1038\/ncomms4017","article-title":"Structural basis of AMPK regulation by small molecule activators","volume":"4","author":"Xiao","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1016\/j.csbj.2021.05.056","article-title":"Structural basis of the selective activation of enzyme isoforms: Allosteric response to activators of beta1- and beta2-containing AMPK complexes","volume":"19","author":"Aledavood","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nature09932","article-title":"Structure of mammalian AMPK and its regulation by ADP","volume":"472","author":"Xiao","year":"2011","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/cr.2014.150","article-title":"Structural basis of AMPK regulation by adenine nucleotides and glycogen","volume":"25","author":"Li","year":"2015","journal-title":"Cell Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s42255-019-0157-1","article-title":"mTORC1 directly inhibits AMPK to promote cell proliferation under nutrient stress","volume":"2","author":"Ling","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1042\/EBC20240007","article-title":"New developments in AMPK and mTORC1 cross-talk","volume":"68","author":"Smiles","year":"2024","journal-title":"Essays Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/j.str.2005.07.008","article-title":"Structural basis for glycogen recognition by AMP-activated protein kinase","volume":"13","author":"Polekhina","year":"2005","journal-title":"Structure"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cmet.2008.11.008","article-title":"The glycogen-binding domain on the AMPK beta subunit allows the kinase to act as a glycogen sensor","volume":"9","author":"McBride","year":"2009","journal-title":"Cell Metab."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Janzen, N.R., Whitfield, J., and Hoffman, N.J. (2018). Interactive Roles for AMPK and Glycogen from Cellular Energy Sensing to Exercise Metabolism. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113344"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1172\/JCI19874","article-title":"CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations","volume":"113","author":"Scott","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.cmet.2013.08.019","article-title":"AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation","volume":"18","author":"Gowans","year":"2013","journal-title":"Cell Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/S0960-9822(03)00249-5","article-title":"A novel domain in AMP-activated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias","volume":"13","author":"Hudson","year":"2003","journal-title":"Curr. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cmet.2017.10.009","article-title":"AMPK: Sensing Glucose as well as Cellular Energy Status","volume":"27","author":"Lin","year":"2018","journal-title":"Cell Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e224","DOI":"10.1038\/emm.2016.16","article-title":"AMPK activators: Mechanisms of action and physiological activities","volume":"48","author":"Kim","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1101\/gad.17420111","article-title":"AMP-activated protein kinase: An energy sensor that regulates all aspects of cell function","volume":"25","author":"Hardie","year":"2011","journal-title":"Genes Dev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cmet.2005.05.009","article-title":"Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase","volume":"2","author":"Hawley","year":"2005","journal-title":"Cell Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"25336","DOI":"10.1074\/jbc.M604399200","article-title":"Mammalian TAK1 activates Snf1 protein kinase in yeast and phosphorylates AMP-activated protein kinase in vitro","volume":"281","author":"Momcilovic","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/emboj.2009.8","article-title":"TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells","volume":"28","author":"Fumarola","year":"2009","journal-title":"EMBO J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Neumann, D. (2018). Is TAK1 a Direct Upstream Kinase of AMPK?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082412"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1172\/JCI29044","article-title":"AMP-activated protein kinase signaling in metabolic regulation","volume":"116","author":"Long","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/joim.12268","article-title":"AMP-activated protein kinase: A key regulator of energy balance with many roles in human disease","volume":"276","year":"2014","journal-title":"J. Intern. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0092-8674(03)00929-2","article-title":"TSC2 mediates cellular energy response to control cell growth and survival","volume":"115","author":"Inoki","year":"2003","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.molcel.2008.03.003","article-title":"AMPK phosphorylation of raptor mediates a metabolic checkpoint","volume":"30","author":"Gwinn","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Peifer-Weiss, L., Al-Hasani, H., and Chadt, A. (2024). AMPK and Beyond: The Signaling Network Controlling RabGAPs and Contraction-Mediated Glucose Uptake in Skeletal Muscle. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031910"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1126\/science.1196371","article-title":"Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy","volume":"331","author":"Egan","year":"2011","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/ncb2757","article-title":"ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase","volume":"15","author":"Russell","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12017","DOI":"10.1073\/pnas.0705070104","article-title":"AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha","volume":"104","author":"Jager","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.tem.2012.06.006","article-title":"Transcriptional integration of mitochondrial biogenesis","volume":"23","author":"Scarpulla","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1126\/science.aab4138","article-title":"Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress","volume":"351","author":"Toyama","year":"2016","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7176","DOI":"10.1038\/ncomms8176","article-title":"AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation","volume":"6","author":"Herms","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"R470","DOI":"10.1016\/j.cub.2015.04.004","article-title":"Expanding roles for lipid droplets","volume":"25","author":"Welte","year":"2015","journal-title":"Curr. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s00109-011-0748-0","article-title":"AMP-activated protein kinase inhibits NF-kappaB signaling and inflammation: Impact on healthspan and lifespan","volume":"89","author":"Salminen","year":"2011","journal-title":"J. Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e0202318","DOI":"10.1128\/MCB.00023-18","article-title":"AMPK Inhibits ULK1-Dependent Autophagosome Formation and Lysosomal Acidification via Distinct Mechanisms","volume":"38","author":"Nwadike","year":"2018","journal-title":"Mol. Cell. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1038\/s41467-023-38401-z","article-title":"Redefining the role of AMPK in autophagy and the energy stress response","volume":"14","author":"Park","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8743","DOI":"10.1038\/s41598-021-87707-9","article-title":"The antiviral effect of metformin on zika and dengue virus infection","volume":"11","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Bhutta, M.S., Gallo, E.S., and Borenstein, R. (2021). Multifaceted Role of AMPK in Viral Infections. Cells, 10.","DOI":"10.3390\/cells10051118"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrm.2017.95","article-title":"AMPK: Guardian of metabolism and mitochondrial homeostasis","volume":"19","author":"Herzig","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5711","DOI":"10.1038\/s41467-020-19287-7","article-title":"MAVS is energized by Mff which senses mitochondrial metabolism via AMPK for acute antiviral immunity","volume":"11","author":"Hanada","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: Molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Silwal, P., Kim, J.K., Yuk, J.M., and Jo, E.K. (2018). AMP-Activated Protein Kinase and Host Defense against Infection. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113495"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e0202016","DOI":"10.1128\/JVI.02020-16","article-title":"Dengue Virus Activates the AMP Kinase-mTOR Axis To Stimulate a Proviral Lipophagy","volume":"91","author":"Jordan","year":"2017","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Soto-Acosta, R., Bautista-Carbajal, P., Cervantes-Salazar, M., Angel-Ambrocio, A.H., and Del Angel, R.M. (2017). DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006257"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e0036018","DOI":"10.1128\/AAC.00360-18","article-title":"Direct Activation of Adenosine Monophosphate-Activated Protein Kinase (AMPK) by PF-06409577 Inhibits Flavivirus Infection through Modification of Host Cell Lipid Metabolism","volume":"62","author":"Blazquez","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"178083","DOI":"10.1016\/j.ejphar.2025.178083","article-title":"Antiviral effect of metformin and phenformin analogs against dengue in Huh-7 cells and AG129 mice","volume":"1005","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Lee, J.K., and Shin, O.S. (2023). Zika virus modulates mitochondrial dynamics, mitophagy, and mitochondria-derived vesicles to facilitate viral replication in trophoblast cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1203645"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.4049\/jimmunol.1901310","article-title":"AMP-Activated Protein Kinase Restricts Zika Virus Replication in Endothelial Cells by Potentiating Innate Antiviral Responses and Inhibiting Glycolysis","volume":"204","author":"Singh","year":"2020","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Simanjuntak, Y., Ko, H.Y., Lee, Y.L., Yu, G.Y., and Lin, Y.L. (2020). Preventive effects of folic acid on Zika virus-associated poor pregnancy outcomes in immunocompromised mice. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008521"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"9841","DOI":"10.1038\/s41467-025-64809-w","article-title":"DISC1 Protects Against Zika Virus Infection and Long-Term Neurological Damage Through AMPK-mTOR-Mediated Autophagy","volume":"16","author":"Zhang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kobayashi, S., Yoshii, K., Phongphaew, W., Muto, M., Hirano, M., Orba, Y., Sawa, H., and Kariwa, H. (2020). West Nile virus capsid protein inhibits autophagy by AMP-activated protein kinase degradation in neurological disease development. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008238"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1186\/s12974-024-03288-0","article-title":"NMDA receptor blockade attenuates Japanese encephalitis virus infection-induced microglia activation","volume":"21","author":"Chang","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e0063524","DOI":"10.1128\/jvi.00635-24","article-title":"Two novel compounds inhibit Flavivirus infection in vitro and in vivo by targeting lipid metabolism","volume":"98","author":"Zhou","year":"2024","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4746","DOI":"10.1038\/s41598-020-61700-0","article-title":"Ginkgolic acid inhibits fusion of enveloped viruses","volume":"10","author":"Borenstein","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jhep.2014.06.031","article-title":"Virology and cell biology of the hepatitis C virus life cycle: An update","volume":"61","author":"Dubuisson","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3350\/cmh.2013.19.1.17","article-title":"Hepatitis C virus: Virology and life cycle","volume":"19","author":"Kim","year":"2013","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11549","DOI":"10.1073\/pnas.0912426107","article-title":"Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase","volume":"107","author":"Mankouri","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1074\/jbc.R111.300202","article-title":"Emerging role of lipid droplets in host\/pathogen interactions","volume":"287","author":"Herker","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"175","DOI":"10.4161\/auto.22791","article-title":"Hepatitis C virus inhibits AKT-tuberous sclerosis complex (TSC), the mechanistic target of rapamycin (MTOR) pathway, through endoplasmic reticulum stress to induce autophagy","volume":"9","author":"Huang","year":"2013","journal-title":"Autophagy"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s12944-019-1136-y","article-title":"Hepatitis C virus nonstructural protein 5A perturbs lipid metabolism by modulating AMPK\/SREBP-1c signaling","volume":"18","author":"Meng","year":"2019","journal-title":"Lipids Health Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"91928","DOI":"10.18632\/oncotarget.20248","article-title":"Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase","volume":"8","author":"Tsai","year":"2017","journal-title":"Oncotarget"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e0201917","DOI":"10.1128\/JVI.02019-17","article-title":"Suppression of Zika Virus Infection and Replication in Endothelial Cells and Astrocytes by PKA Inhibitor PKI 14-22","volume":"92","author":"Cheng","year":"2018","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.ajpath.2019.12.005","article-title":"Hippo Signaling Pathway Has a Critical Role in Zika Virus Replication and in the Pathogenesis of Neuroinflammation","volume":"190","author":"Garcia","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"292","DOI":"10.3390\/metabo2020292","article-title":"5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranosyl 5\u2032-Monophosphate (AICAR), a Highly Conserved Purine Intermediate with Multiple Effects","volume":"2","author":"Pinson","year":"2012","journal-title":"Metabolites"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"110512","DOI":"10.1016\/j.intimp.2023.110512","article-title":"Metformin restrains ZIKV replication and alleviates virus-induced inflammatory responses in microglia","volume":"121","author":"Wang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"14336","DOI":"10.1038\/s41598-019-50674-3","article-title":"Resveratrol affects Zika virus replication in vitro","volume":"9","author":"Mohd","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5379","DOI":"10.1007\/s11033-021-06490-y","article-title":"Antiviral bioactivity of resveratrol against Zika virus infection in human retinal pigment epithelial cells","volume":"48","author":"Russo","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"42998","DOI":"10.1038\/srep42998","article-title":"Resveratrol treatment reveals a novel role for HMGB1 in regulation of the type 1 interferon response in dengue virus infection","volume":"7","author":"Zainal","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Mahalapbutr, P., Hengphasatporn, K., Manimont, W., Vajarintarangoon, L., Shigeta, Y., Bhat, N., Aiebchun, T., Nutho, B., Hannongbua, S., and Rungrotmongkol, T. (2025). Identification of Sulfonamide-Vinyl Sulfone\/Chalcone and Berberine-Cinnamic Acid Hybrids as Potent DENV and ZIKV NS2B\/NS3 Allosteric Inhibitors. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262311762"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.cmet.2010.04.001","article-title":"Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation","volume":"11","author":"Hawley","year":"2010","journal-title":"Cell Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.2337\/diabetes.51.8.2420","article-title":"The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism","volume":"51","author":"Hawley","year":"2002","journal-title":"Diabetes"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.2337\/db05-1188","article-title":"Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice","volume":"55","author":"Zang","year":"2006","journal-title":"Diabetes"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1152\/physrev.00011.2008","article-title":"AMPK in Health and Disease","volume":"89","author":"Steinberg","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Brunton, J., Steele, S., Ziehr, B., Moorman, N., and Kawula, T. (2013). Feeding uninvited guests: mTOR and AMPK set the table for intracellular pathogens. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003552"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Qin, Z.L., Yao, Q.F., Zhao, P., Ren, H., and Qi, Z.T. (2022). Zika virus infection triggers lipophagy by stimulating the AMPK-ULK1 signaling in human hepatoma cells. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.959029"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.chom.2018.05.005","article-title":"Flaviviruses Exploit the Lipid Droplet Protein AUP1 to Trigger Lipophagy and Drive Virus Production","volume":"23","author":"Zhang","year":"2018","journal-title":"Cell Host Microbe"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/8\/910\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T09:34:47Z","timestamp":1787132087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/8\/910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":81,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["v18080910"],"URL":"https:\/\/doi.org\/10.3390\/v18080910","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]}}}