title: BPR-3P0128 inhibits RNA-dependent RNA polymerase elongation and VPg uridylylation activities of Enterovirus 71.
abstract: Enterovirus 71 (EV71) infections can cause hand, foot, and mouth disease with severe neurological complications. Because no clinical drug is available for treating EV71 infections, developing an efficient antiviral medication against EV71 infection is crucial. This study indicated that 6-bromo-2-[1-(2,5-dimethylphenyl)-5-methyl-1H-pyrazol-4-yl] quinoline-4-carboxylic acid (BPR-3P0128) exhibits excellent antiviral activity against EV71 (EC50 = 0.0029 μM). BPR-3P0128 inhibits viral replication during the early post infection stage, targets EV71 RNA-dependent RNA polymerase and VPg uridylylation, and also reduces viral RNA accumulation levels and inhibits viral replication of EV71.
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Arul Balaji
authors.initials: AB
authors.lastname: Velu
authors.affiliation: Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Computer Science and Information Engineering, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Guang-Wu
authors.initials: GW
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Po-Ting
authors.initials: PT
authors.lastname: Hsieh
authors.affiliation: Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences & Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Jim-Tong
authors.initials: JT
authors.lastname: Horng
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Chunan, Taiwan.
authors.forename: John Tsu-An
authors.initials: JT
authors.lastname: Hsu
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Chunan, Taiwan.
authors.forename: Hsing-Pang
authors.initials: HP
authors.lastname: Hsieh
authors.affiliation: Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Tzu-Chun
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Weng
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Clinical Virology Laboratory, Chang Gung Memorial Hospital, Taiwan. Electronic address: srshih@mail.cgu.edu.tw.
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D029821:Enterovirus A, Human / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; C572379:BPR3P0128; D011720:Pyrazoles; D011804:Quinolines; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase
keywords: 3D polymerase inhibitor; EV71-RNA-dependent RNA polymerase (RdRp); VPg uridylylation inhibitor