BPR-3P0128 inhibits RNA-dependent RNA polymerase elongation and VPg uridylylation activities of Enterovirus 71

Arul Balaji Velu; Guang-Wu Chen; Po-Ting Hsieh; Jim-Tong Horng; John Tsu-An Hsu; Hsing-Pang Hsieh; Tzu-Chun Chen; Kuo-Feng Weng; Shin-Ru Shih

doi:10.1016/j.antiviral.2014.10.003

BPR-3P0128 inhibits RNA-dependent RNA polymerase elongation and VPg uridylylation activities of Enterovirus 71

Antiviral Res. 2014 Dec:112:18-25. doi: 10.1016/j.antiviral.2014.10.003. Epub 2014 Oct 18.

Authors

Arul Balaji Velu¹, Guang-Wu Chen², Po-Ting Hsieh¹, Jim-Tong Horng³, John Tsu-An Hsu⁴, Hsing-Pang Hsieh⁴, Tzu-Chun Chen⁵, Kuo-Feng Weng⁵, Shin-Ru Shih⁶

Affiliations

¹ 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.
² 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.
³ 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.
⁴ Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Chunan, Taiwan.
⁵ Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁶ 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.

PMID: 25448086
DOI: 10.1016/j.antiviral.2014.10.003

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.

Keywords: 3D polymerase inhibitor; EV71-RNA-dependent RNA polymerase (RdRp); VPg uridylylation inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / pharmacology*
Cell Line
Cytopathogenic Effect, Viral
Enterovirus A, Human / drug effects*
Enterovirus A, Human / enzymology*
Enterovirus A, Human / physiology
Humans
Inhibitory Concentration 50
Protein Processing, Post-Translational / drug effects*
Pyrazoles / pharmacology*
Quinolines / pharmacology*
RNA-Dependent RNA Polymerase / antagonists & inhibitors*
Viral Plaque Assay
Viral Proteins / metabolism
Virus Replication / drug effects*

Substances

Antiviral Agents
BPR3P0128
Pyrazoles
Quinolines
Viral Proteins
RNA-Dependent RNA Polymerase