TY - JOUR
T1 - Development of a fluorescence resonance energy transfer–based intracellular assay to identify novel enterovirus 71 antivirals
AU - Lu, Wen Wen
AU - Kung, Fang Yen
AU - Deng, Po An
AU - Lin, Yu Chu
AU - Lin, Cheng Wen
AU - Kung, Szu Hao
N1 - Publisher Copyright:
© 2016, Springer-Verlag Wien.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Enterovirus 71 (EV71) is considered one of the most virulent pathogens in the family Picornaviridae. However, there have been no effective treatments for the severe complications caused by EV71. Development of new drugs against targets that are essential for viral replication often requires screening large collections of compounds, for which a high-throughput screening platform is needed. In this study, a drug-screening platform was developed based on a genetically engineered cell line that displays fluorescence resonance energy transfer (FRET) and shows a real-time and quantifiable impairment of FRET upon EV71 infection. A library of small molecules consisting of 1280 compounds with defined bioactivities was used for screening drugs with anti-EV71 activity; accurate, rapid, and robust results were obtained from this screening procedure. Ten drugs were identified in the primary screening, and their antiviral activities were indicated by dose-dependent elevation of FRET. Among these, AC-93253, mitoxantrone and N-bromoacetamide had not been reported as enterovirus inhibitors, and it was confirmed that they were able to suppress viral yields in a dose-dependent manner. Taken together, these studies demonstrate the feasibility of this FRET-based platform for efficient screening and identification of novel compounds with activity against EV71 infection.
AB - Enterovirus 71 (EV71) is considered one of the most virulent pathogens in the family Picornaviridae. However, there have been no effective treatments for the severe complications caused by EV71. Development of new drugs against targets that are essential for viral replication often requires screening large collections of compounds, for which a high-throughput screening platform is needed. In this study, a drug-screening platform was developed based on a genetically engineered cell line that displays fluorescence resonance energy transfer (FRET) and shows a real-time and quantifiable impairment of FRET upon EV71 infection. A library of small molecules consisting of 1280 compounds with defined bioactivities was used for screening drugs with anti-EV71 activity; accurate, rapid, and robust results were obtained from this screening procedure. Ten drugs were identified in the primary screening, and their antiviral activities were indicated by dose-dependent elevation of FRET. Among these, AC-93253, mitoxantrone and N-bromoacetamide had not been reported as enterovirus inhibitors, and it was confirmed that they were able to suppress viral yields in a dose-dependent manner. Taken together, these studies demonstrate the feasibility of this FRET-based platform for efficient screening and identification of novel compounds with activity against EV71 infection.
UR - http://www.scopus.com/inward/record.url?scp=84996508794&partnerID=8YFLogxK
U2 - 10.1007/s00705-016-3143-x
DO - 10.1007/s00705-016-3143-x
M3 - Article
C2 - 27873071
AN - SCOPUS:84996508794
SN - 0304-8608
VL - 162
SP - 713
EP - 720
JO - Archives of Virology
JF - Archives of Virology
IS - 3
ER -