title: Antiviral activity of topoisomerase II catalytic inhibitors against Epstein-Barr virus.
abstract: Herpesviruses require several cellular proteins for their lytic DNA replication including topoisomerase II (Topo II). Thus, Topo II could be an effective drug target against herpesviral infection. In this study, we examined several Topo II catalytic inhibitors for their potentials in blocking EBV replication and becoming efficacious antiviral agents. Topo II catalytic inhibitors in general exhibited marked inhibition of EBV lytic replication and minimal cytotoxicity. In particular, (+)-rutamarin, with the best selectivity index (SI>63) among the inhibitors tested in this study, is effective in inhibiting EBV DNA replication and virion production but shows little adverse effect on cell proliferation, suggesting its potential to become an efficacious and safe drug for the treatment of human diseases associated with EBV infection.
authors.affiliation: Institute of Human Virology, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory of Tropical Disease Control, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Institute of Human Virology, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; Guanghua School of Stomatology, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China. Electronic address: wang93@mail.sysu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Human Virology, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory of Tropical Disease Control, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; Department of Microbiology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA. Electronic address: yuan2@pobox.upenn.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D001578:Benzopyrans / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D001578:Benzopyrans; D004791:Enzyme Inhibitors; C022850:rutamarin; D004250:DNA Topoisomerases, Type II
keywords: (+)-Rutamarin; Antiviral activity; EBV; Merbarone; Novobiocin; Topoisomerases II catalytic inhibitor