title: Repurposing of prochlorperazine for use against dengue virus infection.
abstract: The increasing prevalence of dengue virus (DENV) infection presents serious disease and economic burdens in countries where dengue epidemics are occurring. Despite the clinical importance, no DENV vaccine or anti-DENV drug is available. In this study, we found that prochlorperazine (PCZ), a dopamine D2 receptor (D2R) antagonist approved to treat nausea, vomiting, and headache in humans has potent in vitro and in vivo antiviral activity against DENV infection. PCZ can block DENV infection by targeting viral binding and viral entry through D2R- and clathrin-associated mechanisms, respectively. Administration of PCZ immediately or 6 hours after DENV infection in a Stat1-deficient mouse model completely protected against or delayed lethality. Overall, PCZ showed a previously unknown antiviral effect against DENV infection, and D2R may play a role in the DENV life cycle. Prophylactic and/or therapeutic treatment with PCZ might reduce viral replication and relieve the clinical symptoms of patients with dengue.
authors.affiliation: Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Institute of Biomedical Sciences Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yogy
authors.initials: Y
authors.lastname: Simanjuntak
authors.affiliation: Institute of Biomedical Sciences.
authors.forename: Jian-Jong
authors.initials: JJ
authors.lastname: Liang
authors.affiliation: Institute of Biomedical Sciences.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Institute of Biomedical Sciences Genomic Research Center, Academia Sinica.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lin
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D003715:Dengue / Q000188:drug therapy*; D003716:Dengue Virus / Q000187:drug effects*; D058492:Drug Repositioning / Q000379:methods; D006801:Humans; D051379:Mice; D011346:Prochlorperazine / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011346:Prochlorperazine
keywords: clathrin-mediated endocytosis; dengue virus; dopamine D2 receptor; drug repurposing; prochlorperazine