{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:36:44Z","timestamp":1792805804603,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["200229\/2022-2"],"award-info":[{"award-number":["200229\/2022-2"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"CNPq","award":["200229\/2022-2"],"award-info":[{"award-number":["200229\/2022-2"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["200229\/2022-2"],"award-info":[{"award-number":["200229\/2022-2"]}],"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Financiadora de Estudos e Projetos (FINEP)","award":["200229\/2022-2"],"award-info":[{"award-number":["200229\/2022-2"]}],"id":[{"id":"https:\/\/ror.org\/030w99567","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Zika virus (ZIKV) remains a pressing global health concern due to its association with congenital Zika syndrome and the current lack of approved antiviral therapies. In this study, we evaluated the antiviral activity of three novel thiazolidinedione derivatives, GQ-402, GQ-396, and ZKC-10, against ZIKV in vitro and investigated their potential molecular targets through in silico analysis. GQ-402 exhibited the highest antiviral potency, with an IC50 of 15.7 \u00b5M, while ZKC-10 achieved the most substantial reduction in viral RNA levels, as determined by RT-qPCR. Molecular docking studies identified GQ-396 as the top-ranked inhibitor of the NS2B-NS3 protease and NS5 RNA-dependent RNA polymerase, suggesting distinct mechanisms of action among the compounds. These findings highlight the therapeutic potential of thiazolidinedione derivatives and underscore the need for further investigation to develop effective treatments for ZIKV infection.<\/jats:p>","DOI":"10.3390\/microorganisms13091967","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T11:50:31Z","timestamp":1755863431000},"page":"1967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel Thiazolidinedione Derivatives as Potential ZIKV Antiviral Inhibitors"],"prefix":"10.3390","volume":"13","author":[{"given":"Isabella Luiza","family":"Ralph de Oliveira","sequence":"first","affiliation":[{"name":"Research Center for Therapeutic Innovation Suely Galdino, Federal University of Pernambuco, Recife 50670-901, Brazil"},{"name":"Laboratory of Immunomodulation and New Therapeutic Approaches, Federal University of Pernambuco, Recife 50670-901, 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Threats","volume":"85","author":"Scott","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Halstead, S.B. (2018). Chikungunya and Zika Disease, Elsevier Inc.. Chapter 3.","DOI":"10.1016\/B978-0-12-811865-8.00003-9"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika Virus (I). Isolations and serological specificity","volume":"46","author":"Dick","year":"1952","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_4","unstructured":"European Centre for Disease Prevention and Control (2016). Zika Virus Disease Epidemic: Potential Association with Microcephaly and Guillain-Barre Syndrome (First Update)."},{"key":"ref_5","unstructured":"Pan American Health Organization (PAHO) (2018, January 04). ZIKA Cumulative Cases. Available online: https:\/\/www.paho.org\/en\/documents\/zika-cumulative-cases-4-january-2018."},{"key":"ref_6","first-page":"1395","article-title":"Zika Virus\u2014A Public Health Emergency of International Concern","volume":"73","author":"Roos","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.stem.2016.11.014","article-title":"Advances in Zika Virus Research: Stem Cell Models, Challenges and Opportunities","volume":"19","author":"Ming","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12985-017-0761-1","article-title":"Inhibitors compounds of the flavivirus replication process","volume":"14","author":"Padilla","year":"2017","journal-title":"Virol. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"35207","DOI":"10.1021\/acsomega.3c04903","article-title":"Therapeutic Potential of Antiviral Peptides against the NS2B\/NS3 Protease of Zika Virus","volume":"8","author":"Hossain","year":"2023","journal-title":"ACS Omega"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Fiorucci, D., Meaccini, M., Poli, G., Stincarelli, M.A., Vagaggini, C., Giannecchini, S., Sutto-Ortiz, P., Canard, B., Decroly, E., and Dreassi, E. (2024). Identification of Novel Non-Nucleoside Inhibitors of Zika Virus NS5 Protein Targeting MTase Activity. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042437"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1039\/C8MD00347E","article-title":"Synthesis and antiviral activity of camphor-based 1,3-thiazolidin-4-one and thiazole derivatives as Orthopoxvirus-reproduction inhibitors","volume":"9","author":"Sokolova","year":"2018","journal-title":"MedChemComm"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s41061-020-0298-4","article-title":"Saturated Five-Membered Thiazolidines and Their Derivatives: From Synthesis to Biological Applications","volume":"378","author":"Sahiba","year":"2020","journal-title":"Top. Curr. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.antiviral.2017.08.008","article-title":"Bis(benzofuran-thiazolidinone)s and bis(benzofuran-thiazinanone)s as inhibiting agents for chikungunya virus","volume":"146","author":"Hwu","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105165","DOI":"10.1016\/j.antiviral.2021.105165","article-title":"Inhibitory effect of a novel thiazolidinedione derivative on hepatitis B virus entry","volume":"194","author":"Tanaka","year":"2021","journal-title":"Antivir. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111747","DOI":"10.1016\/j.ejmech.2019.111747","article-title":"Anti-hepatitis-C virus activity and QSAR study of certain thiazolidinone and thiazolotriazine derivatives as potential NS5B polymerase inhibitors","volume":"184","author":"Hassan","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"255","DOI":"10.2174\/1570162X20666220512163049","article-title":"One-Pot Synthesis of Novel Hydrazono-1,3-Th\u0131azol\u0131d\u0131n-4-One Derivatives as Anti-HIV and Anti-Tubercular Agents: Synthes\u0131s, B\u0131olog\u0131cal Evalu- at\u0131on, Molecular Modelling and Admet Stud\u0131es","volume":"20","author":"Zheng","year":"2022","journal-title":"Curr. HIV Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.bbrc.2015.12.042","article-title":"Biochemical and Biophysical Research Communications Discovery of conjugated thiazolidinone-thiadiazole scaffold as anti-dengue virus polymerase inhibitors","volume":"469","author":"Manvar","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Petrou, A., Zagaliotis, P., Theodoroula, N.F., Mystridis, G.A., Vizirianakis, I.S., Walsh, T.J., and Geronikaki, A. (2022). Thiazole\/Thiadiazole\/Benzothiazole Based Thiazolidin-4-One Derivatives as Potential Inhibitors of Main Protease of SARS-CoV-2. Molecules, 27.","DOI":"10.3390\/molecules27072180"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Skore\u0144ski, M., and Sie\u0144czyk, M. (2021). The Fellowship of Privileged Scaffolds\u2014One Structure to Inhibit Them All. Pharmaceuticals, 14.","DOI":"10.3390\/ph14111164"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7767","DOI":"10.2174\/0929867328666210629152929","article-title":"Exploiting Dengue Virus Protease as a Therapeutic Target: Current Status, Challenges and Future Avenues","volume":"28","author":"Mushtaq","year":"2021","journal-title":"Curr Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.2174\/1389557521666211101154619","article-title":"A critical observation on the design and development of reported peptide inhibitors of DENV NS2B-NS3 protease in the last two decades","volume":"22","author":"Murtuja","year":"2022","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jitonnom, J., Meelua, W., Tue-Nguen, P., Saparpakorn, P., Hannongbua, S., and Chotpatiwetchkul, W. (2024). 3D-QSAR and molecular docking studies of peptide-hybrids as dengue virus NS2B\/NS3 protease inhibitors. Chem. Biol. Interact., 396.","DOI":"10.1016\/j.cbi.2024.111040"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Starvaggi, J., Previti, S., Zappal\u00e0, M., and Ettari, R. (2024). The Inhibition of NS2B\/NS3 Protease: A New Therapeutic Opportunity to Treat Dengue and Zika Virus Infection. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084376"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.2174\/0115680266315388240801053401","article-title":"Evaluation of thiazolidine derivatives with potential anti-ZIKV activity","volume":"24","author":"Galdino","year":"2024","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"de Oliveira, M.C.V.A., Viana, D.C.F., Silva, A.A., Pereira, M.C., Duarte, F.S., Pitta, M.G.R., Pitta, I.R., and Pitta, M.G.R. (2022). Bioorganic Chemistry Synthesis of novel thiazolidinic-phthalimide derivatives evaluated as new multi-target antiepileptic agents. Bioorganic Chem., 119.","DOI":"10.1016\/j.bioorg.2021.105548"},{"key":"ref_26","unstructured":"Moura, J.A.d.S. (Federal University of Pernambuco, Recife, Pernambuco, Brazil), Unpublished work, 2023."},{"key":"ref_27","unstructured":"Branco Junior (Federal University of Pernambuco, Recife, Pernambuco, Brazil), Unpublished work, 2017."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6504","DOI":"10.1021\/jm050543p","article-title":"Modeling Water Molecules in Protein\u2014Ligand Docking Using GOLD","volume":"48","author":"Verdonk","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/S0968-0896(01)00366-2","article-title":"Synthesis and aldose reductase inhibitory activity of 5-arylidene-2,4-thiazolidinediones","volume":"10","author":"Bruno","year":"2002","journal-title":"Bioorg. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1021\/jm800937p","article-title":"Synthesis and Evaluation of Novel Inhibitors of Pim-1 and Pim-2 Protein Kinases","volume":"52","author":"Xia","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2008.05.003","article-title":"Flavivirus methyltransferase: A novel antiviral target","volume":"80","author":"Dong","year":"2008","journal-title":"Antivir. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.antiviral.2009.11.009","article-title":"Structure and functionality in flavivirus NS-proteins: Perspectives for drug design","volume":"87","author":"Bollati","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wei, Y., Li, J., Qing, J., Huang, M., Wu, M., Gao, F., Li, D., Hong, Z., Kong, L., and Huang, W. (2016). Discovery of Novel Hepatitis C Virus NS5B Polymerase Inhibitors by Combining Random Forest, Multiple e-Pharmacophore Modeling and Docking. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148181"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1007\/s00044-017-1815-z","article-title":"Synthesis and biological evaluation of novel anti-hepatitis C virus (HCV) agents: 2-hydroxylphenethyl sulfanyl-oxopyrimidines","volume":"26","author":"Wu","year":"2017","journal-title":"Med. Chem. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kaptein, F., and Neyts, J. (2016). The Viral Polymerase Inhibitor 7-Deaza-2\u2019\u2014C-Methyladenosine Is a Potent Inhibitor of In Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model. PLoS Neglected Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004695"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gonzalez, S., Brzuska, G., Ouarti, A., Gallier, F., Solarte, C., Ferry, A., Uziel, J., Krol, E., and Lubin-Germain, N. (2022). Bioorganic & Medicinal Chemistry Anti-HCV and Zika activities of ribavirin C -nucleosides analogues. Bioorganic Med. Chem., 68.","DOI":"10.1016\/j.bmc.2022.116858"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2017.08.007","article-title":"Ribavirin inhibits Zika virus (ZIKV) replication in vitro and suppresses viremia in ZIKV-infected STAT1-deficient mice","volume":"146","author":"Kamiyama","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6851","DOI":"10.3390\/cimb45080433","article-title":"Recent Advances in Molecular Mechanisms of Nucleoside Antivirals","volume":"45","author":"Kamzeeva","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Qian, X., and Qi, Z. (2022). Mosquito-Borne Flaviviruses and Current Therapeutic Advances. Viruses, 14.","DOI":"10.3390\/v14061226"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bassetto, M., Cima, C.M., Basso, M., Salerno, M., Schwarze, F., Friese, D., Bugert, J.J., and Brancale, A. (2020). Novel Nucleoside Analogues as Effective Antiviral Agents for Zika Virus Infections. Molecules, 25.","DOI":"10.3390\/molecules25204813"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/01480545.2019.1620264","article-title":"The improved antiviral activities of amino- modified chitosan derivatives on Newcastle virus The improved antiviral activities of amino-modified chitosan derivatives on","volume":"44","author":"He","year":"2019","journal-title":"Drug Chem. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4764","DOI":"10.1021\/jm3002247","article-title":"Design, Synthesis, and Antiviral Activity of Entry Inhibitors That Target the CD4-Binding Site of HIV-1","volume":"55","author":"Curreli","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1093\/bib\/bby061","article-title":"Recent applications of deep learning and machine intelligence on in silico drug discovery: Methods, tools and databases","volume":"20","author":"Rifaioglu","year":"2019","journal-title":"Brief. Bioinform."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0022-2836(82)90153-X","article-title":"A Geometric Approach to Macromolecule-Ligand Interactions","volume":"161","author":"Kuntz","year":"1982","journal-title":"J. Mol. Biol."},{"key":"ref_45","first-page":"1597","article-title":"Crystal structure of unlinked NS2B-NS3 protease from Zika virus","volume":"354","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11348","DOI":"10.1021\/cr500233q","article-title":"Biochemistry and Medicinal Chemistry of the Dengue Virus Protease","volume":"114","author":"Nitsche","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_47","first-page":"1743","article-title":"Families of cysteine peptidases","volume":"244","author":"Rawlings","year":"1994","journal-title":"Methods Enzymol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.antiviral.2015.03.014","article-title":"The flavivirus NS2B\u2014NS3 protease\u2014Helicase as a target for antiviral drug development","volume":"118","author":"Luo","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nsmb1073","article-title":"Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus","volume":"13","author":"Erbel","year":"2006","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"108036","DOI":"10.1016\/j.dib.2022.108036","article-title":"The data on molecular docking of cinnamic acid amide on dengue viral target NS2B\/NS3","volume":"42","author":"Mohamed","year":"2022","journal-title":"Data Brief"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.2174\/1568026623666221122121330","article-title":"Advances in Computational Methods to Discover New NS2B-NS3 Inhibitors Useful Against Dengue and Zika Viruses","volume":"22","year":"2022","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Kumar, S., El-Kafrawy, S.A., Bharadwaj, S., Maitra, S.S., Alandijany, T.A., Faizo, A.A., Khateb, A.M., Dwivedi, V.D., and Azhar, E.I. (2022). Discovery of Bispecific Lead Compounds from Azadirachta indica against ZIKA NS2B-NS3 Protease and NS5 RNA Dependent RNA Polymerase Using Molecular Simulations. Molecules, 27.","DOI":"10.3390\/molecules27082562"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1021\/acs.jcim.1c01326","article-title":"Characterization of an Allosteric Pocket in Zika Virus NS2B-NS3 Protease","volume":"62","author":"Lei","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"ref_54","first-page":"1525","article-title":"Inhibition of Dengue Virus Protease by Eugeniin, Isobiflorin, and Biflorin Isolated from the Flower Buds of Syzygium aromaticum (Cloves)","volume":"4","author":"Saleem","year":"2019","journal-title":"Am. Chem. Soc."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/9\/1967\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:33:54Z","timestamp":1760034834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/9\/1967"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,22]]},"references-count":54,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["microorganisms13091967"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13091967","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,22]]}}}