title: Quinacrine impairs enterovirus 71 RNA replication by preventing binding of polypyrimidine-tract binding protein with internal ribosome entry sites.
abstract: Since the 1980s, epidemics of enterovirus 71 (EV71) and other enteroviruses have occurred in Asian countries and regions, causing a wide range of human diseases. No effective therapy is available for the treatment of these infections. Internal ribosome entry sites (IRESs) are indispensable for the initiation of translation in enteroviruses. Several cellular factors, as well as the ribosome, are recruited to the conserved IRES during this process. Quinacrine intercalates into the RNA architecture and inhibits RNA transcription and protein synthesis, and a recent study showed that quinacrine inhibited encephalomyocarditis virus and poliovirus IRES-mediated translation in vitro without disrupting internal cellular IRES. Here, we report that quinacrine was highly active against EV71, protecting cells from EV71 infection. Replication of viral RNA, expression of viral capsid protein, and production of virus were all strongly inhibited by quinacrine. Interaction of the polypyrimidine tract-binding protein (PTB) with the conserved IRES was prevented by quinacrine. Coxsackieviruses and echovirus were also inhibited by quinacrine in cultured cells. These results indicate that quinacrine may serve as a potential protective agent for use in the treatment of patients with chronic enterovirus infection.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.forename: Jiang
authors.initials: J
authors.lastname: Du
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D029821:Enterovirus A, Human / Q000378:metabolism*; D004769:Enterovirus Infections / Q000188:drug therapy; D006801:Humans; D020128:Inhibitory Concentration 50; D010957:Plasmids / Q000378:metabolism; D038941:Polypyrimidine Tract-Binding Protein / Q000737:chemistry* / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000821:virology; D012270:Ribosomes / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D034741:RNA, Small Interfering; D012367:RNA, Viral; D038941:Polypyrimidine Tract-Binding Protein; D011796:Quinacrine