{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:58:32Z","timestamp":1787029112189,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T00:00:00Z","timestamp":1670198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2019A1515010681"],"award-info":[{"award-number":["2019A1515010681"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["82130101"],"award-info":[{"award-number":["82130101"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2019B020202002"],"award-info":[{"award-number":["2019B020202002"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["ZZ13-035-02"],"award-info":[{"award-number":["ZZ13-035-02"]}]},{"name":"National Natural Science Foundation of China","award":["2019A1515010681"],"award-info":[{"award-number":["2019A1515010681"]}]},{"name":"National Natural Science Foundation of China","award":["82130101"],"award-info":[{"award-number":["82130101"]}]},{"name":"National Natural Science Foundation of China","award":["2019B020202002"],"award-info":[{"award-number":["2019B020202002"]}]},{"name":"National Natural Science Foundation of China","award":["ZZ13-035-02"],"award-info":[{"award-number":["ZZ13-035-02"]}]},{"name":"The Major scientific and technological projects of Guangdong Province","award":["2019A1515010681"],"award-info":[{"award-number":["2019A1515010681"]}]},{"name":"The Major scientific and technological projects of Guangdong Province","award":["82130101"],"award-info":[{"award-number":["82130101"]}]},{"name":"The Major scientific and technological projects of Guangdong Province","award":["2019B020202002"],"award-info":[{"award-number":["2019B020202002"]}]},{"name":"The Major scientific and technological projects of Guangdong Province","award":["ZZ13-035-02"],"award-info":[{"award-number":["ZZ13-035-02"]}]},{"name":"Construction Project of Influenza Prevention and Treatment Technology System of Chinese Medicine organized by Chinese Academy of Traditional Chinese Medicine","award":["2019A1515010681"],"award-info":[{"award-number":["2019A1515010681"]}]},{"name":"Construction Project of Influenza Prevention and Treatment Technology System of Chinese Medicine organized by Chinese Academy of Traditional Chinese Medicine","award":["82130101"],"award-info":[{"award-number":["82130101"]}]},{"name":"Construction Project of Influenza Prevention and Treatment Technology System of Chinese Medicine organized by Chinese Academy of Traditional Chinese Medicine","award":["2019B020202002"],"award-info":[{"award-number":["2019B020202002"]}]},{"name":"Construction Project of Influenza Prevention and Treatment Technology System of Chinese Medicine organized by Chinese Academy of Traditional Chinese Medicine","award":["ZZ13-035-02"],"award-info":[{"award-number":["ZZ13-035-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Dengue fever is the most common mosquito-borne viral disease and is caused by the dengue virus (DENV). There is still a lack of efficient drugs against DENV infection, so it is urgent to develop new inhibitors for future clinical use. Our previous research indicated the role of VEGFR2\/AMPK in regulating cellular metabolism during DENV infection, while acetyl-CoA carboxylase (ACC) is located downstream of AMPK and plays a crucial role in mediating cellular lipid synthesis; therefore, we speculated that an ACC inhibitor could serve as an antiviral agent against DENV. Luckily, we found that CP640186, a reported noncompetitive ACC inhibitor, significantly inhibited DENV proliferation, and CP640186 clearly reduced DENV2 proliferation at an early stage with an EC50 of 0.50 \u03bcM. A mechanism study indicated that CP640186 inhibited ACC activation and destroyed the cellular lipid environment for viral proliferation. In the DENV2 infection mice model, oral CP640186 administration (10 mg\/kg\/day) significantly improved the mice survival rate after DENV2 infection. In summary, our research suggests that lipid synthesis plays an important role during DENV2 proliferation and indicates that CP640186 is a promising drug candidate against DNEV2 in the future.<\/jats:p>","DOI":"10.3390\/molecules27238583","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T09:46:45Z","timestamp":1670233605000},"page":"8583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Acetyl-CoA Carboxylase (ACC) Inhibitor, CP640186, Effectively Inhibited Dengue Virus (DENV) Infection via Regulating ACC Phosphorylation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8189-2850","authenticated-orcid":false,"given":"Wenyu","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilin","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanda","family":"Wan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liren","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyun","family":"Lei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-5006","authenticated-orcid":false,"given":"Shuwen","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1950-6576","authenticated-orcid":false,"given":"Xingang","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.antiviral.2013.09.013","article-title":"Ten years of dengue drug discovery: Progress and prospects","volume":"100","author":"Lim","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/S0140-6736(14)61060-6","article-title":"Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: A phase 3, randomised, observer-masked, placebo-controlled trial","volume":"384","author":"Capeding","year":"2014","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1437","DOI":"10.1002\/wrna.1437","article-title":"Organization of the Flavivirus RNA replicase complex","volume":"8","author":"Brand","year":"2017","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Uchida, L., Urata, S., Ulanday, G.E.L., Takamatsu, Y., Yasuda, J., Morita, K., and Hayasaka, D. (2016). Suppressive Effects of the Site 1 Protease (S1P) Inhibitor, PF-429242, on Dengue Virus Propagation. Viruses, 8.","DOI":"10.3390\/v8020046"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105121","DOI":"10.1016\/j.antiviral.2021.105121","article-title":"The novel therapeutic target and inhibitory effects of PF-429242 against Zika virus infection","volume":"192","author":"Raini","year":"2021","journal-title":"Antivir. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/ncb1631","article-title":"The lipid droplet is an important organelle for hepatitis C virus production","volume":"9","author":"Miyanari","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105721","DOI":"10.1016\/j.phrs.2021.105721","article-title":"Brivanib alaninate inhibited dengue virus proliferation through VEGFR2\/AMPK pathway","volume":"170","author":"Wan","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Russell, P.K., Brandt, W.E., and Dalrymple, J.M. (1980). Chemical and antigenic structure of flaviviruses. The Togaviruses, Elsevier.","DOI":"10.1016\/B978-0-12-625380-1.50023-0"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1089\/vim.2014.0095","article-title":"Protein Disulfide Isomerase Mediates Dengue Virus Entry in Association with Lipid Rafts","volume":"28","author":"Diwaker","year":"2015","journal-title":"Viral Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.chom.2010.10.006","article-title":"Dengue Virus-Induced Autophagy Regulates Lipid Metabolism","volume":"8","author":"Heaton","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/nature07976","article-title":"Autophagy regulates lipid metabolism","volume":"458","author":"Singh","year":"2009","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"17345","DOI":"10.1073\/pnas.1010811107","article-title":"Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis","volume":"107","author":"Heaton","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12985-017-0685-9","article-title":"Involvement of fatty acid synthase in dengue virus infection","volume":"14","author":"Tongluan","year":"2017","journal-title":"Virol. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5434","DOI":"10.1158\/1078-0432.CCR-15-0126","article-title":"Molecular Pathways: Fatty Acid Synthase","volume":"21","author":"Jones","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1038\/nm.3372","article-title":"Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin","volume":"19","author":"Fullerton","year":"2013","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.cmet.2017.09.018","article-title":"Acetyl-CoA Carboxylase 1-Dependent Protein Acetylation Controls Breast Cancer Metastasis and Recurrence","volume":"26","author":"Steinbauer","year":"2017","journal-title":"Cell Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1080\/13543784.2019.1657825","article-title":"Acetyl-CoA carboxylase (ACC) as a therapeutic target for metabolic syndrome and recent developments in ACC1\/2 inhibitors","volume":"28","author":"Chen","year":"2019","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.jhep.2020.04.037","article-title":"Acetyl-CoA carboxylase inhibition disrupts metabolic reprogramming during hepatic stellate cell activation","volume":"73","author":"Bates","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1080\/22221751.2019.1604084","article-title":"Targeting host metabolism by inhibition of acetyl-Coenzyme A carboxylase reduces flavivirus infection in mouse models","volume":"8","author":"Esler","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1128\/AAC.01578-15","article-title":"Modification of the Host Cell Lipid Metabolism Induced by Hypolipidemic Drugs Targeting the Acetyl Coenzyme A Carboxylase Impairs West Nile Virus Replication","volume":"60","author":"Casas","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"37099","DOI":"10.1074\/jbc.M304481200","article-title":"Isozyme-nonselective N-substituted bipiperidylcarboxamide acetyl-CoA carboxylase inhibitors reduce tissue malonyl-CoA concentrations, inhibit fatty acid synthesis, and increase fatty acid oxidation in cultured cells and in experimental animals","volume":"278","author":"Harwood","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.antiviral.2016.07.003","article-title":"Liver-specific mono-unsaturated fatty acid synthase-1 inhibitor for anti-hepatitis C treatment","volume":"132","author":"Nio","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ejphar.2017.12.029","article-title":"Inhibition of dengue viral infection by diasarone-I is associated with 2\u2019O methyltransferase of NS5","volume":"821","author":"Yao","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1016\/j.str.2004.07.009","article-title":"Crystal Structure of the Carboxyltransferase Domain of Acetyl-Coenzyme A Carboxylase in Complex with CP-640186","volume":"12","author":"Zhang","year":"2004","journal-title":"Structure"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1002\/jcb.21077","article-title":"Acetyl-coenzyme A carboxylases: Versatile targets for drug discovery","volume":"99","author":"Tong","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41401-019-0316-7","article-title":"[1,2,4]Triazolo[1,5-a]pyrimidine derivative (Mol-5) is a new NS5-RdRp inhibitor of DENV2 proliferation and DENV2-induced inflammation","volume":"41","author":"Wan","year":"2019","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_29","first-page":"258","article-title":"Tatanan A from the Acorus calamus L. root inhibited dengue virus proliferation and infections","volume":"42","author":"Yao","year":"2018","journal-title":"Phytomedicine Int. J. Phytother. Phytopharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jphs.2018.06.012","article-title":"Q63, a novel DENV2 RdRp non-nucleoside inhibitor, inhibited DENV2 replication and infection","volume":"138","author":"Yao","year":"2018","journal-title":"J. Pharmacol. Sci."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/23\/8583\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:34:33Z","timestamp":1760146473000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/23\/8583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,5]]},"references-count":30,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["molecules27238583"],"URL":"https:\/\/doi.org\/10.3390\/molecules27238583","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,5]]}}}