Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening  

作　　者：Qiu-Yan Zhang Jia-Qi Li Qi Li Yang Zhang Zhe-Rui Zhang Xiao-Dan Li Hong-Qing Zhang Cheng-Lin Deng Feng-Xia Yang Yi Xu Bo Zhang 

机构地区：[1]The Joint Center of Translational Precision Medicine,Department of Infections and Diseases,Guangzhou Institute of Pediatrics,Guangzhou Women and Children's Medical Center,Guangzhou,510623,China [2]Key Laboratory of Special Pathogens and Biosafety,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,430071,China [3]University of Science and Technology of China,Department of Life Sciences and Medicine,Hefei,230026,China [4]Hunan Normal University,School of Medicine,Changsha,410081,China

出　　处：《Virologica Sinica》2024年第2期301-308,共8页中国病毒学（英文版）

基　　金：funded by Guangzhou Municipal Science and Technology Project(202102020241);the National Natural Science Foundation of China(32100110 and 32300132);the National Key Research and Development Program of China(2021YFC2701800,2021YFC2701801).

摘　　要：Hand,foot,and mouth disease(HFMD)is a common pediatric illness mainly caused by enteroviruses,which are important human pathogens.Currently,there are no available antiviral agents for the therapy of enterovirus infection.In this study,an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed.Using this screening system,we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors.Fangchinoline(FAN),a bis-benzylisoquinoline alkaloid,exhibits potential inhibitory effects against various enteroviruses that cause HFMD,such as EV-A71,CV-A10,CV-B3 and CV-A16.Further investigations revealed that FAN targets the early stage of the enterovirus life cycle.Through the selection of FAN-resistant EV-A71 viruses,we demonstrated that the VP1 protein could be a potential target of FAN,as two mutations in VP1(E145G and V258I)resulted in viral resistance to FAN.Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

关 键 词：Hand foot and mouth disease(HFMD) ENTEROVIRUS EV-A71 High-content screening Fangchinoline(FAN) 

分 类 号：R978.7[医药卫生—药品]