Identification of three antiviral inhibitors against Japanese encephalitis virus from library of pharmacologically active compounds 1280

PloS One
Jin'e FangYunfeng Song

Abstract

Japanese encephalitis virus (JEV) can cause severe central nervous disease with a high mortality rate. There is no antiviral drug available for JEV-specific treatment. In this study, a cytopathic-effect-based, high-throughput screening assay was developed and applied to screen JEV inhibitors from Library of Pharmacologically Active Compounds 1280. The antiviral effects of three hit compounds including FGIN-1-27, cilnidipine, and niclosamide were evaluated in cells by western blotting, indirect immunofluorescence assay, and plaque reduction assay. A time-of-addition assay proved that all three compounds inhibited JEV at the stage of replication. The EC50s of FGIN-1-27, cilnidipine, and niclosamide were 3.21, 6.52, and 5.80 µM, respectively, while the selectivity indexes were 38.79, 30.67, and 7.49. FGIN-1-27 and cilnidipine have high efficiency and selectivity against JEV. This study provided two JEV antiviral inhibitors as candidates for treatment of JEV infection.

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Citations

Sep 28, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Rachel P M AbramsAvindra Nath
Jul 12, 2018·Expert Opinion on Biological Therapy·Luisa Barzon, Giorgio Palù
Apr 27, 2018·Nature Reviews. Neurology·Lance Turtle, Tom Solomon
Dec 25, 2019·Antimicrobial Agents and Chemotherapy·Jiao GuoWei Wang
Aug 1, 2020·Antibiotics·José Diogo SantosOlga Maria Lage
Jan 11, 2019·Scientific Reports·José A Marrugal-LorenzoJavier Sánchez-Céspedes
Jul 17, 2019·Current Drug Discovery Technologies·Khojasteh MalekmohammadRobert D E Sewell
Dec 31, 2020·Viruses·Stephen D Carro, Sara Cherry
Feb 23, 2020·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Petter I AndersenDenis E Kainov
Mar 4, 2020·ACS Infectious Diseases·Jimin XuJia Zhou

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Methods Mentioned

BETA
Assay
fluorescence resonance energy transfer

Software Mentioned

ImageJ

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