Antiviral research · 2016
Novel antiviral activity of bromocriptine against dengue virus replication.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Kato Fumihiro, Ishida Yuki, Oishi Shinya, Fujii Nobutaka, Watanabe Satoru, Vasudevan Subhash G, Tajima Shigeru, Takasaki Tomohiko, Suzuki Youichi, Ichiyama Koji, Yamamoto Naoki, Yoshii Kentaro, Takashima Ikuo, Kobayashi Takeshi, Miura Tomoyuki, Igarashi Tatsuhiko, Hishiki Takayuki
Аннотация
Dengue virus (DENV) infectious disease is a major public health problem worldwide; however, licensed vaccines or specific antiviral drugs against this infection are not available. To identify novel anti-DENV compounds, we screened 1280 pharmacologically active compounds using focus reduction assay. Bromocriptine (BRC) was found to have potent anti-DENV activity and low cytotoxicity (half maximal effective concentration [EC50], 0.8-1.6 μM; and half maximal cytotoxicity concentration [CC50], 53.6 μM). Time-of-drug-addition and time-of-drug-elimination assays suggested that BRC inhibits translation and/or replication steps in the DENV life cycle. A subgenomic replicon system was used to verify that BRC restricts RNA replication step. Furthermore, a single amino acid substitution (N374H) was detected in the NS3 protein that conferred resistance to BRC. In summary, BRC was found to be a novel DENV inhibitor and a potential candidate for the treatment of DENV infectious disease.