Development of drugs targeting hepatitis B x-protein

开发针对乙型肝炎x蛋白的药物

• 批准号: 24659359
• 负责人: SAKAMOTO NAOYA
• 金额: $ 2.41万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659359/
• 关键词: ウイルス; 医学; ウイルス学; 基礎研究; B型肝炎

We have conducted study project to develop new classes of antiviral drug against hepatitis B virus (HBV). In the study period, we obtained the following results. (1) HBV expression plasmid which selectively lacks HBX protein showed decreased expression levels as compared with wild type when transfected into humans hepatoma Huh7 cells. (2) Mutant HBV expression plasmids were constructed in which 4 consecutive alanine substitution were introduced in the HBX protein coding frame. By using the mutant HBX plasmids, we found AP1 transactivator domain in C-terminal of HBX.

我们开展了开发新型抗乙肝病毒药物的研究项目。在研究期间，我们取得了以下成果。(1)与野生型相比，选择性缺失HBx蛋白的HBx表达载体在人肝癌Huh7细胞中的表达水平明显降低。(2)构建了HBx蛋白编码框中连续引入4个丙氨酸取代的突变型乙肝病毒表达载体。利用突变的HBx质粒，我们在HBx的C端发现了AP1反式激活域。

项目成果

A new method for induced fit docking (GENIUS) and its application to virtual screening of novel HCV NS3-4A protease inhibitors

诱导拟合对接新方法（GENIUS）及其在新型HCV NS3-4A蛋白酶抑制剂虚拟筛选中的应用

• DOI: 10.1016/j.bmc.2011.09.023
• 发表时间: 2011
• 期刊: Bioorganic & Medicinal Chemistry
• 影响因子: 3.5
• 作者: Takaya D;Sakamoto N;et al.
• 通讯作者: et al.

Ochanomizu Liver Conference Study Group : Association of ITPA gene variant and serum ribavirin concentration with blood cells decline in pegylated interferon-alfa plus ribavirin therapy for chronic hepatitis C

Ochanomizu 肝脏会议研究组：ITPA 基因变异和血清利巴韦林浓度与聚乙二醇干扰素-α加利巴韦林治疗慢性丙型肝炎中血细胞下降的关系

• 发表时间: 2012
• 期刊: Hepatol Int
• 影响因子: 6.6
• 作者: Nakagawa M;Sakamoto N;Watanabe T;Nishimura-Sakurai Y;Onozuka I;Azuma S;Kakinuma S;Nitta S;Kiyohashi K;Kusano-Kitazume A;Murakawa M;Yoshino K;Itsui Y;Tanaka Y;Mizokami M;Watanabe M.
• 通讯作者: Watanabe M.

Age and total ribavirin dose are independent predictors of relapse after interferon therapy in chronic hepatitis C revealed by data mining analysis

• DOI: 10.3851/imp1923
• 发表时间: 2012-01-01
• 期刊: ANTIVIRAL THERAPY
• 影响因子: 1.2
• 作者: Kurosaki, Masayuki;Hiramatsu, Naoki;Izumi, Namiki
• 通讯作者: Izumi, Namiki

Inhibition of both protease and helicase activities of hepatitis C virus NS3 by an ethyl acetate extract of marine sponge Amphimedon sp.

• DOI: 10.1371/journal.pone.0048685
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Fujimoto Y;Salam KA;Furuta A;Matsuda Y;Fujita O;Tani H;Ikeda M;Kato N;Sakamoto N;Maekawa S;Enomoto N;de Voogd NJ;Nakakoshi M;Tsubuki M;Sekiguchi Y;Tsuneda S;Akimitsu N;Noda N;Yamashita A;Tanaka J;Moriishi K
• 通讯作者: Moriishi K

Analysis of the complete open reading frame of hepatitis C virus in genotype 2a infection reveals critical sites influencing the response to peginterferon and ribavirin therapy

• DOI: 10.1007/s12072-011-9267-x
• 发表时间: 2011-09-01
• 期刊: HEPATOLOGY INTERNATIONAL
• 影响因子: 6.6
• 作者: Kadokura, Makoto;Maekawa, Shinya;Enomoto, Nobuyuki
• 通讯作者: Enomoto, Nobuyuki