Novel antiviral activity of bromocriptine against dengue virus replication

• Published in: Antiviral research Vol. 131; pp. 141 - 147
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Netherlands 01.07.2016
• Subjects: Antiviral Agents - pharmacology; Bromocriptine - pharmacology; Dengue - drug therapy; Dengue virus; Dengue Virus - drug effects; Dengue Virus - physiology; Drug Resistance, Viral; Humans; Replicon - drug effects; Viral Plaque Assay; Virus Replication - drug effects; Time-of-drug addition; Focus assay; Antiviral drug; Dengue virus; Bromocriptine; Replicon
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2016.04.014

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.