{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:44:44Z","timestamp":1786985084632,"version":"build-2736575974"},"reference-count":31,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100007300","name":"China Medical University","doi-asserted-by":"publisher","award":["CMU-DDCCENTER-TD3-2"],"award-info":[{"award-number":["CMU-DDCCENTER-TD3-2"]}],"id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007300","name":"China Medical University","doi-asserted-by":"publisher","award":["CMU112-MF-26"],"award-info":[{"award-number":["CMU112-MF-26"]}],"id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007300","name":"China Medical University","doi-asserted-by":"publisher","award":["CMU113-ASIA-11"],"award-info":[{"award-number":["CMU113-ASIA-11"]}],"id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006379","name":"Office of Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006379","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["111-2923-B-039-001-MY3"],"award-info":[{"award-number":["111-2923-B-039-001-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSTC112-2320-B-039-054-MY3"],"award-info":[{"award-number":["NSTC112-2320-B-039-054-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2025,5]]},"DOI":"10.1016\/j.bcp.2025.116839","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T02:32:25Z","timestamp":1740709945000},"page":"116839","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Darunavir inhibits dengue virus replication by targeting the hydrophobic pocket of the envelope protein"],"prefix":"10.1016","volume":"235","author":[{"given":"Ju-Ying","family":"Kan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jen","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsueh-Chou","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Hsuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Wen","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-Yi","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Wen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bcp.2025.116839_b0005","unstructured":"WHO, Dengue and severe dengue. Retrieved from https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dengue-and-severe-dengue; 2020."},{"key":"10.1016\/j.bcp.2025.116839_b0010","doi-asserted-by":"crossref","DOI":"10.1016\/j.virusres.2022.199018","article-title":"Dengue virus infection - a review of pathogenesis, vaccines, diagnosis and therapy","volume":"324","author":"Kok","year":"2023","journal-title":"Virus Res.,"},{"key":"10.1016\/j.bcp.2025.116839_b0015","doi-asserted-by":"crossref","DOI":"10.1016\/j.modpat.2023.100188","article-title":"Flaviviruses and the Traveler: Around the World and to Your Stage. A Review of West Nile, Yellow Fever, Dengue, and Zika Viruses for the Practicing Pathologist","volume":"36","author":"Hale","year":"2023","journal-title":"Mod Pathol.,"},{"key":"10.1016\/j.bcp.2025.116839_b0020","doi-asserted-by":"crossref","first-page":"150","DOI":"10.3390\/tropicalmed5040150","article-title":"Dengue and Zika Viruses: Epidemiological History, Potential Therapies, and Promising Vaccines","volume":"5","author":"Silva","year":"2020","journal-title":"Trop Med Infect Dis.,"},{"key":"10.1016\/j.bcp.2025.116839_b0025","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1016\/j.sjbs.2021.05.023","article-title":"Dengue and human health: A global scenario of its occurrence, diagnosis and therapeutics","volume":"28","author":"Sabir","year":"2021","journal-title":"Saudi J Biol Sci."},{"key":"10.1016\/j.bcp.2025.116839_b0030","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1200195","article-title":"Dengue virus neutralizing antibody: a review of targets, cross-reactivity, and antibody-dependent enhancement","volume":"14","author":"Sarker","year":"2023","journal-title":"Front Immunol.,"},{"key":"10.1016\/j.bcp.2025.116839_b0035","first-page":"615","article-title":"Flavivirus: From Structure to Therapeutics Development","volume":"11","author":"Zhao","year":"2021","journal-title":"Life (basel)"},{"key":"10.1016\/j.bcp.2025.116839_b0040","doi-asserted-by":"crossref","first-page":"705","DOI":"10.3390\/v15030705","article-title":"Molecular Mechanisms of Antiviral Agents against Dengue Virus","volume":"15","author":"Lee","year":"2023","journal-title":"Viruses"},{"key":"10.1016\/j.bcp.2025.116839_b0045","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s12985-021-01611-2","article-title":"The key amino acids of E protein involved in early flavivirus infection: viral entry","volume":"18","author":"Hu","year":"2021","journal-title":"Virol J.,"},{"key":"10.1016\/j.bcp.2025.116839_b0050","doi-asserted-by":"crossref","first-page":"6986","DOI":"10.1073\/pnas.0832193100","article-title":"A ligand-binding pocket in the dengue virus envelope glycoprotein","volume":"100","author":"Modis","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"10.1016\/j.bcp.2025.116839_b0055","doi-asserted-by":"crossref","unstructured":"A.H. S, G.V. Pujar, A.K. Sethu, Bhagyalalitha M, Singh M. Dengue structural proteins as antiviral drug targets: Current status in the drug discovery & development. Eur. J. Med. Chem., 221 (2021) 113527.","DOI":"10.1016\/j.ejmech.2021.113527"},{"key":"10.1016\/j.bcp.2025.116839_b0060","doi-asserted-by":"crossref","first-page":"e428","DOI":"10.1371\/journal.pone.0000428","article-title":"Combinatorial computational approaches to identify tetracycline derivatives as flavivirus inhibitors","volume":"2","author":"Yang","year":"2007","journal-title":"PLoS One"},{"key":"10.1016\/j.bcp.2025.116839_b0065","first-page":"681","article-title":"Study the antiviral activity of some derivatives of tetracycline and non-steroid anti-inflammatory drugs towards dengue virus","volume":"30","author":"Rothan","year":"2013","journal-title":"Trop Biomed"},{"key":"10.1016\/j.bcp.2025.116839_b0070","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1093\/infdis\/jiu377","article-title":"Repurposing of prochlorperazine for use against dengue virus infection","volume":"211","author":"Simanjuntak","year":"2015","journal-title":"J Infect Dis.,"},{"key":"10.1016\/j.bcp.2025.116839_b0075","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2020.606743","article-title":"Repurposing the Antiemetic Metoclopramide as an Antiviral Against Dengue Virus Infection in Neuronal Cells","volume":"10","author":"Shen","year":"2021","journal-title":"Front Cell Infect Microbiol.,"},{"key":"10.1016\/j.bcp.2025.116839_b0080","first-page":"461","article-title":"A Review Concerning the Use of Etravirine and Darunavir in Translational Medicine","volume":"3","author":"Pereira","year":"2023","journal-title":"Int. J. Transl. Med.,"},{"key":"10.1016\/j.bcp.2025.116839_b0085","doi-asserted-by":"crossref","unstructured":"M. Mahdi, J.A. M\u00f3ty\u00e1n, Z.I. Szojka, M. Golda, M. Miczi, J. T\u0151zs\u00e9r, Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2\u2019s main protease. Virol. J., 17 (2020):190.","DOI":"10.1186\/s12985-020-01457-0"},{"key":"10.1016\/j.bcp.2025.116839_b0090","doi-asserted-by":"crossref","DOI":"10.1016\/j.jmgm.2022.108193","article-title":"The SARS-CoV-2 helicase as a target for antiviral therapy: Identification of potential small molecule inhibitors by in silico modelling","volume":"114","author":"Pitsillou","year":"2022","journal-title":"J Mol Graph Model.,"},{"key":"10.1016\/j.bcp.2025.116839_b0095","article-title":"Identification of potential antivirals against SARS-CoV-2 using virtual screening method","volume":"23","author":"Rahman","year":"2021","journal-title":"Inform Med Unlocked.,"},{"key":"10.1016\/j.bcp.2025.116839_b0100","article-title":"Darunavir ethanolate: Repurposing an anti-HIV drug in COVID-19 treatment","volume":"3","author":"Chavda","year":"2021","journal-title":"Eur J Med Chem Rep.,"},{"key":"10.1016\/j.bcp.2025.116839_b0105","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.2165\/00003495-200464180-00014","article-title":"Fosamprenavir: a review of its use in the management of antiretroviral therapy-naive patients with HIV infection","volume":"64","author":"Chapman","year":"2004","journal-title":"Drugs"},{"key":"10.1016\/j.bcp.2025.116839_b0110","doi-asserted-by":"crossref","first-page":"5723","DOI":"10.1128\/AAC.00748-11","article-title":"TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows in vitro an improved resistance profile and higher genetic barrier to resistance compared with current protease inhibitors","volume":"55","author":"Dierynck","year":"2011","journal-title":"Antimicrob Agents Chemother.,"},{"key":"10.1016\/j.bcp.2025.116839_b0115","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1128\/AAC.00401-07","article-title":"In vitro antiviral activity of the novel, tyrosyl-based human immunodeficiency virus (HIV) type 1 protease inhibitor brecanavir (GW640385) in combination with other antiretrovirals and against a panel of protease inhibitor-resistant HIV","volume":"51","author":"Hazen","year":"2007","journal-title":"Antimicrob Agents Chemother.,"},{"key":"10.1016\/j.bcp.2025.116839_b0120","doi-asserted-by":"crossref","first-page":"10309","DOI":"10.3390\/ijms231810309","article-title":"Glycyrrhizic Acid Derivatives Bearing Amino Acid Residues in the Carbohydrate Part as Dengue Virus E Protein Inhibitors: Synthesis and Antiviral Activity","volume":"23","author":"Hour","year":"2022","journal-title":"Int J Mol Sci.,"},{"key":"10.1016\/j.bcp.2025.116839_b0125","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.3390\/biomedicines11102754","article-title":"The Antiviral Activity of Varenicline against Dengue Virus Replication during the Post-Entry Stage","volume":"11","author":"Lin","year":"2023","journal-title":"Biomedicines"},{"key":"10.1016\/j.bcp.2025.116839_b0130","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2024.129623","article-title":"Inhibition of dengue viruses by N-methylcytisine thio derivatives through targeting viral envelope protein and NS2B-NS3 protease","volume":"99","author":"Lin","year":"2024","journal-title":"Bioorg Med Chem Lett.,"},{"key":"10.1016\/j.bcp.2025.116839_b0135","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3390\/v9040076","article-title":"Single-Round Infectious Particle Antiviral Screening Assays for the Japanese Encephalitis Virus","volume":"9","author":"Lu","year":"2017","journal-title":"Viruses"},{"key":"10.1016\/j.bcp.2025.116839_b0140","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/sj.emboj.7600064","article-title":"Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation","volume":"23","author":"Bressanelli","year":"2004","journal-title":"EMBO J.,"},{"key":"10.1016\/j.bcp.2025.116839_b0145","first-page":"8250","article-title":"Progress in the identification of dengue virus entry\/fusion inhibitors","volume":"1","author":"De La Guardia","year":"2014","journal-title":"Biomed Res Int.,"},{"key":"10.1016\/j.bcp.2025.116839_b0150","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116465","article-title":"Antiviral drug discovery: Pyrimidine entry inhibitors for Zika and dengue viruses","volume":"272","author":"Gallo","year":"2024","journal-title":"Eur J Med Chem.,"},{"key":"10.1016\/j.bcp.2025.116839_b0155","doi-asserted-by":"crossref","unstructured":"E.S. Leal, N.S. Adler, G.A. Fern\u00e1ndez, L.G. Gebhard, L. Battini, M.G. Aucar, M. Videla, M.E. Monge, A. Hern\u00e1ndez de Los R\u00edos, J. A. Acosta D\u00e1vila, M. L. Morell, S. M. Cordo, C. C. Garc\u00eda, A.V. Gamarnik, C.N. Cavasotto, M. Bollini, De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus. Eur J Med Chem., 182 (2019) 111628.","DOI":"10.1016\/j.ejmech.2019.111628"}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295225001017?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295225001017?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T12:05:48Z","timestamp":1753445148000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295225001017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":31,"alternative-id":["S0006295225001017"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2025.116839","relation":{},"ISSN":["0006-2952"],"issn-type":[{"value":"0006-2952","type":"print"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Darunavir inhibits dengue virus replication by targeting the hydrophobic pocket of the envelope protein","name":"articletitle","label":"Article Title"},{"value":"Biochemical Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bcp.2025.116839","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"116839"}}