宿主・ウイルスを標的とした抗HCV薬剤・化合物の大規模スクリーニング

• 研究課題/領域番号: 21390226
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 消化器内科学
• 研究機関: 東京医科歯科大学
• 研究代表者: 坂本 直哉 東京医科歯科大学, 大学院・医歯学総合研究科, 寄附講座教員 (10334418)
• 研究分担者: 中川 美奈 東京医科歯科大学, 医学部附属病院, 助教 (30401342) ; 東 正新 東京医科歯科大学, 医学部附属病院, 助教 (10376783) ; 渡辺 守 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (10175127)
• 連携研究者: 藤田 めぐみ (田坂 めぐみ) 東京医科歯科大学, 大学院・医歯学総合研究科, 特任助教 (50510369)
• 研究期間 (年度): 2009 – 2011
• 研究課題ステータス: 完了 (2011年度)
• 配分額: 17,810千円 (直接経費: 13,700千円、間接経費: 4,110千円); 2011年度: 5,200千円 (直接経費: 4,000千円、間接経費: 1,200千円); 2010年度: 5,980千円 (直接経費: 4,600千円、間接経費: 1,380千円); 2009年度: 6,630千円 (直接経費: 5,100千円、間接経費: 1,530千円)
• キーワード: C型肝炎 / レプリコンシステム / HCV-Feoレプリコン / HCV-JFH1培養系 / 小分子ライブラリー

研究概要

我々はHCV増殖に関連する宿主因子の探索を遂行し、以下の結果を得た。(1) replicon細胞を用いて8, 000種の化合物ライブラリーから5個のエポキシ誘導体を同定した。(2) 4, 000種の化合物をスクリーニングし、HCV感染を抑制する5種の化合物を同定した。(3) SRタンパクキナーゼを標的とした抗HCV分子4個を同定した。以上の知見より、新規クラス抗HCV療法薬剤の開発を目標に引き続き研究を遂行する。

研究成果

• [雑誌論文] Suppression of hepatitis C virus replicon by adenovirus vector-mediated expression of tough decoy RNA against miR-122a. Virus Research (2012)
  • 著者名/発表者名: Sakurai F, Furukawa N, Higuchi M, Okamoto S, Ono K, Yoshida T, Kondoh M, Yagi K, Sakamoto N, Katayama K, Mizuguchi H
  • 雑誌名: EPub ahead of Print 巻: 165 号: 2 ページ: 214-218
  • DOI: 10.1016/j.virusres.2012.02.003
  • 査読あり
• [雑誌論文] Let-7b is a novel regulator of hepatitis C virus replication. Cell Mol Life Sci 2012 (2012)
  • 著者名/発表者名: Cheng J-C, Yeh YJ, Tseng CP, Hsu SD, Chang YL, Sakamoto N, Huang HD
  • 雑誌名: EPub ahead of Print 巻: 69 号: 15 ページ: 2621-2633
  • DOI: 10.1007/s00018-012-0940-6
  • 査読あり
• [雑誌論文] Inhibition of hepatitis C virus NS5B polymerase by S-trityl-L-cysteine derivatives (2012)
  • 著者名/発表者名: Nichols DB, Fournet G, Gurukumar KR, Basu A, Lee JC, Sakamoto N, Kozielski F, Musmuca I, Joseph B, Ragno R, Kaushik-Basu N
  • 雑誌名: Eur J MedChem 巻: 49 ページ: 191-199
• [雑誌論文] Identification of novel N-(morpholine-4-carbonyloxy) amidine compounds as potent inhibitors against hepatitis C virus replication (2012)
  • 著者名/発表者名: Kusano-Kitazume A, Sakamoto N, Okuno Y, Sekine-Osajima Y, Nakagawa M, Kakinuma S, Kiyonashi K, Nitta S, Murakawa M, Azuma S, Nishimura-Sakurai Y, Hagiwara M, Watanabe M
  • 雑誌名: Antimicrob Agent Chemother 巻: 56(3) ページ: 1315-1323
• [雑誌論文] Inhibition of hepatitis C virus NS5B polymerase by S-trityl-L-cysteine derivatives (2012)
  • 著者名/発表者名: Kaushik-Basu N, Sakamoto N
  • 雑誌名: Eur J Med Chem 巻: 49 ページ: 191-199
  • DOI: 10.1016/j.ejmech.2012.01.010
  • 査読あり
• [雑誌論文] Age and total ribavirin dose are independent predictors of relapse after interferon therapy in chronic hepatitis C revealed by data mining analysis (2012)
  • 著者名/発表者名: Kurosaki M, Sakamoto N, Nakagawa M, et al.
  • 雑誌名: Antivir Ther 巻: 17(1) ページ: 35-43
  • 査読あり
• [雑誌論文] Data mining model using simple and readily available factors could identify patients at high risk for hepatocellular carcinoma in chronic hepatitis C (2012)
  • 著者名/発表者名: Kurosaki M, Sakamoto N, Nakagawa M, et al.
  • 雑誌名: J Hepatol 巻: 56(3) 号: 3 ページ: 602-608
  • DOI: 10.1016/j.jhep.2011.09.011
  • 査読あり
• [雑誌論文] Use of human hepatocyte-like cells derived from induced pluripotent stem cells as a model for hepatocytes in hepatitis C virus infection (2011)
  • 著者名/発表者名: Yoshida T, Takayama K, Kondoh M, Sakurai F, Tani H, Sakamoto N, Matsuura Y, Mizuguchi H, Yagi K
  • 雑誌名: Biochem Biophys Res Commun 巻: 416(1-2) ページ: 119-124
• [雑誌論文] A new method for induced fit docking(GENIUS) and its application to virtual screening of novel HCV NS3-4A protease inhibitors (2011)
  • 著者名/発表者名: Takaya D, Yamashita A, Kamijo K, Gomi J, Ito M, Maekawa S, Enomoto N, SakamotoN, Watanabe Y, Arai R, Umeyama H, Honma T, Matsumoto T, Yokoyama S
  • 雑誌名: Bioorganic & Medicinal Chemistry 巻: 19(22) ページ: 6892-6905
• [雑誌論文] Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylatedinterferon and ribavirin therapy for chronic hepatitis C (2011)
  • 著者名/発表者名: Tanaka Y, Kurosaki M, Nishida N, Sugiyama M, Matsuura K, Sakamoto N, Enomoto N, Yatsuhashi H, Nishiguchi S, Hino K, Hige S, Itoh Y, Tanaka E, Mochida S, Honda M, Hiasa Y, Koike A, Sugauchi F, Kaneko S, Izumi N, Tokunaga K, Mizokami M
  • 雑誌名: Human Molecular Genetics 巻: 20(17) ページ: 3507-3516
• [雑誌論文] Analysis of the complete open reading frame of genotype 2b hepatitis C virus inassociation with the response to peginterferon and ribavirin therapy (2011)
  • 著者名/発表者名: Kadokura M, Maekawa S, Sueki R, Miura M, Komase K, Shindo H, Amemiya F, Uetake T, Inoue T, Sakamoto M, Nakagawa M, Sakamoto N, Watanabe M, Enomoto N
  • 雑誌名: PLoSOne 巻: 6(9)
• [雑誌論文] Adenovirus vector-mediated assay system for hepatitis C virus replication (2011)
  • 著者名/発表者名: Yoshida T, Kondoh M, Ojima M, Mizuguchi H, Yamagishi Y, Sakamoto N, Yagi K
  • 雑誌名: Nucleic Acids Res 巻: 39(10)
• [雑誌論文] Analysis of interferon signaling by infectious hepatitis C virus clones with substitutions of core amino acids 70 and 91 (2011)
  • 著者名/発表者名: Funaoka Y, Sakamoto N, Nakagawa M, Kakinuma S, Suda S, Watanabe T, Nitta S, Kitazume A, Kiyohashi K, Murakawa M, Azuma S, Tsuchiya K, and Watanabe M
  • 雑誌名: J Virol 巻: 85(12) ページ: 5986-5994
• [雑誌論文] The inhibitory effect on hepatitis C virus infection of a triterpenoid compound, with or without interferon-alpha (2011)
  • 著者名/発表者名: Watanabe T, Sakamoto N, Nakagawa M, Kakinuma S, Itsui Y, Nishimura-Sakurai Y, Ueyama M, Funaoka Y, Kitazume A, Nitta S, Kiyohashi K, Murakawa M, Azuma S, Tsuchiya K, Oooka S, Watanabe M
  • 雑誌名: Antimicrob Agents Chemother 巻: 55(6) ページ: 2537-2545
• [雑誌論文] Studies on virus kinetics using infectious fluorescence-tagged hepatitis C virus cell culture (2011)
  • 著者名/発表者名: Yamamoto M, Sakamoto N, Nakamura T, Itsui Y, Nakagawa M, Nishimura-Sakurai Y, Kakinuma S, Azuma S, Tsuchiya K, Kato T, Wakita T, Watanabe M
  • 雑誌名: Hepatol Res 巻: 41 ページ: 258-269
• [雑誌論文] Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes (2011)
  • 著者名/発表者名: Toyoda M, Kitaoka A, Machida K, Nishinakagawa T, Yada R, Kohjima M, Kato M, Kotoh K, Sakamoto N, Shiota G, Nakamuta M, Nakashima M, Enjoji M
  • 雑誌名: Int J Mol Med 巻: 27 ページ: 619-624
• [雑誌論文] Association of gene expression involving innate immunity and genetic variation in IL28B with antiviral response (2011)
  • 著者名/発表者名: Asahina Y, Sakamoto N, et al.
  • 雑誌名: Hepatology 巻: 55(1) ページ: 20-29
  • 査読あり
• [雑誌論文] 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 (2011)
  • 著者名/発表者名: Kadokura M, Nakagawa M, Sakamoto N, Watanabe M, et al.
  • 雑誌名: Hepatol Int 巻: 5(3) 号: 3 ページ: 789-799
  • DOI: 10.1007/s12072-011-9267-x
  • 査読あり
• [雑誌論文] A new method for induced fit docking (GENIUS) and its application to virtual screening of novel HCV NS3-4A protease inhibitors (2011)
  • 著者名/発表者名: Takaya D, Sakamoto N, et al.
  • 雑誌名: Bioorganic & Medicinal Chemistry 巻: 19(22) 号: 22 ページ: 6892-6905
  • DOI: 10.1016/j.bmc.2011.09.023
  • 査読あり
• [雑誌論文] Serum interleukin-6 levels correlate with resistance to treatment of chronic hepatitis C infection with pegylated-interferon-alpha2b plus ribavirin (2011)
  • 著者名/発表者名: Ueyama M, Nakagawa M, Sakamoto N, et al.
  • 雑誌名: Antivir Ther 巻: 16 ページ: 1081-1091
  • 査読あり
• [雑誌論文] Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylated interferon and ribavirin therapy for chronic hepatitis C (2011)
  • 著者名/発表者名: Tanaka Y, Sakamoto N, et al.
  • 雑誌名: Human Molecular Genetics 巻: 20(17) 号: 17 ページ: 3507-3516
  • DOI: 10.1093/hmg/ddr249
  • 査読あり
• [雑誌論文] Pretreatment Prediction of Anemia Progression by Peginterferon Plus Ribavirin Therapy in Chronic Hepatitis C : Decision-Tree Analysis (2011)
  • 著者名/発表者名: Hiramatsu N, Sakamoto N, et al.
  • 雑誌名: J Gastroenterol 巻: 46(9) 号: 9 ページ: 1111-1119
  • DOI: 10.1007/s00535-011-0412-z
  • 査読あり
• [雑誌論文] Analysis of the complete open reading frame of genotype 2b hepatitis C virus in association with the response to peginterferon and ribavirin therapy (2011)
  • 著者名/発表者名: Kadokura M, Nakagawa M, Sakamoto N, Watanabe M, et al.
  • 雑誌名: PLoS One 巻: 6(9) 号: 9 ページ: e24514-e24514
  • DOI: 10.1371/journal.pone.0024514
  • 査読あり
• [雑誌論文] Pretreatment prediction of response to peginterferon plus ribavirin therapy in genotype 1 chronic hepatitis C using data mining analysis (2011)
  • 著者名/発表者名: Kurosaki M, Sakamoto N, et al.
  • 雑誌名: J Gastroenterol 巻: 46(3) 号: 3 ページ: 401-409
  • DOI: 10.1007/s00535-010-0322-5
  • NAID: 10029028096
  • 査読あり
• [雑誌論文] Adenovirus vector-mediated assay system for hepatitis C virus replication (2011)
  • 著者名/発表者名: Yoshida T, Sakamoto N, et al.
  • 雑誌名: Nucleic Acids Res 巻: 39(10)
  • 査読あり
• [雑誌論文] Inhibitory effect of a triterpenoid compound, with or without alpha interferon, on hepatitis C virus infection (2011)
  • 著者名/発表者名: Watanabe T, Sakamoto N, Nakagawa M, Azuma S, Watanabe M, et al.
  • 雑誌名: Antimicrob Agents Chemother 巻: 55(6) 号: 6 ページ: 2537-2545
  • DOI: 10.1128/aac.01780-10
  • 査読あり
• [雑誌論文] Association of IL28B variants with response to pegylated-interferon alpha plus ribavirin combination therapy reveals intersubgenotypic differences between genotypes 2a and 2b (2011)
  • 著者名/発表者名: Sakamoto N, Nakagawa M, Azuma S, Watanabe M, et al.
  • 雑誌名: J Med Virol 巻: 83 号: 5 ページ: 871-878
  • DOI: 10.1002/jmv.22038
  • 査読あり
• [雑誌論文] Cholestatic liver fibrosis and toxin-induced fibrosis are exacerbated in matrix metalloproteinase-2 deficient mice (2011)
  • 著者名/発表者名: Onozuka I, Sakamoto N, Nakagawa M, Watanabe M, et al.
  • 雑誌名: Biochem Biophys Res Commun 巻: 406 号: 1 ページ: 134-140
  • DOI: 10.1016/j.bbrc.2011.02.012
  • 査読あり
• [雑誌論文] Pre-treatment prediction of response to pegylated-interferon plus ribavirin for chronic hepatitis C using genetic polymorphism in IL28B and viral factors (2011)
  • 著者名/発表者名: Kurosaki M, Sakamoto N, Nakagawa M, Watanabe M, et al.
  • 雑誌名: J Hepatol 巻: 54 号: 3 ページ: 439-448
  • DOI: 10.1016/j.jhep.2010.07.037
  • 査読あり
• [雑誌論文] Sequences in the interferon sensitivity-determining region and core region of hepatitis C virus impact pretreatment prediction of response to PEG-interferon plus ribavirin : data mining analysis (2011)
  • 著者名/発表者名: Kurosaki M, Sakamoto N, Nakagawa M, et al.
  • 雑誌名: J Med Virol 巻: 83 号: 3 ページ: 445-452
  • DOI: 10.1002/jmv.22005
  • 査読あり
• [雑誌論文] Association between hpid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes. (2011)
  • 著者名/発表者名: Tbyoda M, Kitaoka A, Machida K, Nishinakagawa T, Yada R, Kohjima M, Kato M, Kotoh K, Sakamoto N, et al.
  • 雑誌名: Int J Mol Med 巻: (EPub ahead of print)
  • 査読あり
• [雑誌論文] Serum interleukin-6 levels can predict resistance to treatment of chronic hepatitis C infection with pegylated-interferon alpha 2b plus ribavirin. (2011)
  • 著者名/発表者名: Mayumi Ueyama, Mina Nakagawa, Naova Sakamoto, Seishin Azuma, Mamoru Watanabe, et al.
  • 雑誌名: Antivral Therapy 巻: in press
  • 査読あり
• [雑誌論文] Adenovirus vector-mediated assay system for Hepatitis C virus replication. (2011)
  • 著者名/発表者名: Takeshi Yoshida, Masuo Kondoh, Manabu Ojima, Hiroyuki Mizuguchi, Naova Sakalnoto
  • 雑誌名: Nucl Acid Res 巻: (EPub ahead of print)
  • 査読あり
• [雑誌論文] Association of IL28B polymorphism with response to pegylated-interferon alpha plus ribavirin combination therapy in patients with chronic genotype 2 hepatitis C. (2011)
  • 著者名/発表者名: Naova Sakamoto, et al.
  • 雑誌名: JMedical Virol 巻: in press
  • 査読あり
• [雑誌論文] Studies on virus kinetics using injbctious fluorescence-tagged hepatitis C ViruS Cell Culture. (2011)
  • 著者名/発表者名: Machi Yamamoto, Naoya Sakamoto, et al.
  • 雑誌名: Hepatology Research 巻: in press
  • 査読あり
• [雑誌論文] Sequences in the Interferon Sensitivity Determining Region and Core Region of Hepatitis C Virus Impact Pretreatment Prediction of Response to Peg-interferon Plus Ribavirin : Data Mining Analysis. (2011)
  • 著者名/発表者名: Masayuki Kurosaki, Naoya Sakamoto, Manabu Iwasaki, Minoru Sakamoto, et al.
  • 雑誌名: J Medical Virol 巻: in press
  • 査読あり
• [雑誌論文] Pretreatment Prediction of response to peginterferon plus ribavirin in chronic hepatitis C using data mining analysis. (2011)
  • 著者名/発表者名: Masayuki Kurosaki, Naoya Sakamoto, et al.
  • 雑誌名: J Gastroenterol 巻: in press
  • 査読あり
• [雑誌論文] IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis C virus genotype 2a/2b chimeric clones (2010)
  • 著者名/発表者名: Suda G, Sakamoto N, Itsui Y, Nakagawa M, Tasaka-Fujita M, Funaoka Y, Watanabe T, Nitta S, Kiyohashi K, Azuma S, Kakinuma S, Tsuchiya K, Imamura M, Hiraga N, Chayama K, Watanabe M
  • 雑誌名: Virology 巻: 407 ページ: 80-90
• [雑誌論文] ITPA gene variant protects against anemia induced by pegylated interferon-alpha and ribavirin therapy for Japanese patients with chronic hepatitis C (2010)
  • 著者名/発表者名: Sakamoto N, Tanaka Y, Nakagawa M, Yatsuhashi H, Nishiguchi S, Enomoto N, Azuma S, Nishimura-Sakurai Y, Kakinuma S, Nishida N, Tokunaga K, Honda M, Ito K, Mizokami M, Watanabe M
  • 雑誌名: Hepatol Res 巻: 40 ページ: 1063-1071
• [雑誌論文] Cell culture and in vivo analyses of cytopathic hepatitis C virus mutants (2010)
  • 著者名/発表者名: Mishima K, Sakamoto N, Sekine-Osajima Y, Nakagawa M, Itsui Y, Azuma S, Kakinuma S, Kiyohashi K, Kitazume A, Tsuchiya K, Imamura M, Hiraga N, Chayama K, Wakita T, Watanabe M
  • 雑誌名: Virology 巻: 405 ページ: 361-369
• [雑誌論文] Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1 pathway (2010)
  • 著者名/発表者名: Kim K, Kim KH, Kim HY, Cho HK, Sakamoto N, Cheong J
  • 雑誌名: FEBS Lett 巻: 584 ページ: 707-712
• [雑誌論文] Inhibition of hepatitis C virus replication by a specific inhibitor of serine-arginine-rich protein kinase (2010)
  • 著者名/発表者名: Karakama Y, Sakamoto N, Itsui Y, Nakagawa M, Tasaka-Fujita M, Nishimura-Sakurai Y, Kakinuma S, Oooka M, Azuma S, Tsuchiya K, Onogi H, Hagiwara M, Watanabe M
  • 雑誌名: Antimicrob Agents Chemother 巻: 54 ページ: 3179-3186
• [雑誌論文] Pretreatment Prediction of Response to Pegylated-Interferon Plus Ribavirin for Chronic Hepatitis C using Genetic Polymorphism in IL28B and Viral Factors. (2010)
  • 著者名/発表者名: Masayuki Kurosaki, Yasuhito Tanaka, Nao Nishida, Masaya Sugiyama, Naoya Sakamoto, et al.
  • 雑誌名: J Hepatol 巻: (EPub)
  • 査読あり
• [雑誌論文] ITPA gene variant protects against anemia induced by pegylated interferon-alfa and ribavirin therapy for Japanese patients with chronichepatitis C (2010)
  • 著者名/発表者名: Naova Sakamoto, Yasuhito Tanaka, et al.
  • 雑誌名: Hepatology Research 巻: 40 ページ: 1063-1071
  • 査読あり
• [雑誌論文] IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis C virus genotype 2a/2b chimeric clones. (2010)
  • 著者名/発表者名: Goki Suda, Naova Sakamoto, et al.
  • 雑誌名: Virology 巻: 407 ページ: 80-90
  • 査読あり
• [雑誌論文] Inhibition of HCV replication by a specific inhibitor of serin-arginine-rich protein kinase. (2010)
  • 著者名/発表者名: Yuko Karakama,Naoya Sakamoto, et al.
  • 雑誌名: Antimicrobial Agent and Chemotherapy 巻: 54 ページ: 3179-3186
  • 査読あり
• [雑誌論文] Cen culture and in-vivo analyses of plaque-derived cytopathic hepatitis C Vlrus mutants. (2010)
  • 著者名/発表者名: Kako Mishima, Naova Sakamoto, et al
  • 雑誌名: Virology 巻: 405 ページ: 361-369
  • 査読あり
• [雑誌論文] Mutations in the Interferon Sensitivity Determining Region and virological response to combination therapy with Pegylated-interferon alpha 2b plusribavirin in patients with chronic hepatitis C-1b infection. (2010)
  • 著者名/発表者名: Mina Nakagawa, Naoya Sakamoto, et al.
  • 雑誌名: JGastroenterol 巻: 45 ページ: 656-665
  • 査読あり
• [雑誌論文] Comparison of HCVLassociated gene expression and cell signaling pathways in cells with or without HCV replicon and in replicon-cured cells. (2010)
  • 著者名/発表者名: Yuki Nishimura-Sakurai, Naoya Sakamoto, et al.
  • 雑誌名: JGastroentorol 巻: 45 ページ: 523-536
  • 査読あり
• [雑誌論文] Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1pathway (2010)
  • 著者名/発表者名: KyeongJin Kim, Kook Hwan Kim, Hye Ybung Kim, Hyun Kook Cho, Naova Sakamoto, et al.
  • 雑誌名: FEBS Letter 巻: 584 ページ: 707-712
  • 査読あり
• [雑誌論文] Inhibition of hepatitis C virus replication by chloroquine targeting virus'associated autophagy. (2010)
  • 著者名/発表者名: Tomokazu Mizui, Shunhei Yamashina, Isei Tanida, MotokiTakashima, Naova Sakamoto, etal.
  • 雑誌名: J Gastroenterol 巻: 5 ページ: 195-203
  • 査読あり
• [雑誌論文] Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1 pathway. (2010)
  • 著者名/発表者名: Kim K, Sakamoto N, et al
  • 雑誌名: FEBS Lett. 584 ページ: 707-712
  • 査読あり
• [雑誌論文] Mutations in the Interferon Sensitivity Determining Region and virological response to combination therapy with Pegylated-interferon alpha 2b plus ribavirin in patients with chronic hepatitis C-1b infection. (2010)
  • 著者名/発表者名: Nakagawa M, Sakamoto N(equal contribution), et al
  • 雑誌名: J Gastroenterol (in press)
  • NAID: 10027216778
  • 査読あり
• [雑誌論文] Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq (2009)
  • 著者名/発表者名: Wang SY, Tseng CP, Tsai KC, Lin CF, Wen CY, Tsay HS, Sakamoto N, Tseng CH, Cheng JC
  • 雑誌名: Biochem BiophysRes Commun 巻: 385 ページ: 230-235
• [雑誌論文] Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C (2009)
  • 著者名/発表者名: Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M
  • 雑誌名: NatGenet 巻: 41 ページ: 1105-1109
• [雑誌論文] A functional genomic screen identifies cellular cofactors of hepatitis C virus replication (2009)
  • 著者名/発表者名: Tai AW, Benita Y, Peng LF, Kim SS, Sakamoto N, Xavier RJ, Chung RT
  • 雑誌名: Cell Host Microbe 巻: 5 ページ: 298-307
• [雑誌論文] Two flavonoids extracts from Glycyrrhizae radix inhibit in vitro hepatitis C virus replication (2009)
  • 著者名/発表者名: Sekine-Osajima Y, Sakamoto N, Nakagawa M, Itsui Y, Tasaka M, Nishimura-Sakurai Y, Chen CH, Suda G, Mishima K, Onuki Y, Yamamoto M, Maekawa S, Enomoto N, Kanai T, Tsuchiya K, Watanabe M
  • 雑誌名: Hepatol Res 巻: 39 ページ: 60-69
  • NAID: 10025324061
• [雑誌論文] Prospects for future therapy of hepatitis Cvirus infection (2009)
  • 著者名/発表者名: Sakamoto N, Wu GY
  • 雑誌名: Future Virology 巻: 4 ページ: 453-462
• [雑誌論文] New therapeutic approaches to hepatitis Cvirus (2009)
  • 著者名/発表者名: Sakamoto N, Watanabe M
  • 雑誌名: JGastroenterol 巻: 44 ページ: 643-649
  • NAID: 10025175879
• [雑誌論文] Antiviral effects of the interferon-induced protein guanylate binding protein 1 and its interaction with the hepatitis C virus NS5B protein (2009)
  • 著者名/発表者名: Itsui Y, Sakamoto N, Kakinuma S, Nakagawa M, Sekine-Osajima Y, Tasaka-Fujita M, Nishimura-Sakurai Y, Suda G, Karakama Y, Mishima K, Yamamoto M, Watanabe T, Ueyama M, Funaoka Y, Azuma S, Watanabe M
  • 雑誌名: Hepatology 巻: 50 ページ: 1727-1737
• [雑誌論文] The isomerase active site of cyclophilin A is critical for hepatitis C virus replication (2009)
  • 著者名/発表者名: Chatterji U, Bobardt M, Selvarajah S, Yang F, Tang H, Sakamoto N, Vuagniaux G, Parkinson T, Gallay P
  • 雑誌名: J Biol Chem 巻: 284 ページ: 16998-17005
• [雑誌論文] Comparison of HCV-associated gene expression and cell signaling pathways in cells with or without HCV replicon and in replicon-cured cells. (2009)
  • 著者名/発表者名: Nishimura-Sakurai Y, Sakamoto N, et al
  • 雑誌名: J Gastroentorol (EPub)
  • NAID: 10027216127
  • 査読あり
• [雑誌論文] Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy. (2009)
  • 著者名/発表者名: Mizui T, Sakamoto N, et al
  • 雑誌名: J Gastroenterol 45 ページ: 195-203
  • NAID: 10027214573
  • 査読あり
• [雑誌論文] Antiviral effects of the interferon-induced protein GBP-1 and its interaction with the hepatitis C virus NS5B protein. (2009)
  • 著者名/発表者名: Itsui Y, Sakamoto N(equal contribution), et al
  • 雑誌名: Hepatology 50 ページ: 1727-1737
  • 査読あり
• [雑誌論文] Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. (2009)
  • 著者名/発表者名: Tanaka Y, Sakamoto N, et al
  • 雑誌名: Nature Genetics 41 ページ: 1105-1109
  • 査読あり
• [雑誌論文] Hepatitis C virus NS5A protein increases hepatic lipid accumulation via induction of activation and expression of PPARgamma. (2009)
  • 著者名/発表者名: Kim K, Sakamoto N, et al
  • 雑誌名: FEBS Letter 583 ページ: 2720-2726
  • 査読あり
• [雑誌論文] IL-7 is Essential for Lymphopenia-driven Turnover of Colitogenic CD4+ Memory T Cells in Chronic Colitis. (2009)
  • 著者名/発表者名: Tomita T, Sakamoto N, et al
  • 雑誌名: Eur J Immuno 39 ページ: 2737-2747
  • 査読あり
• [雑誌論文] Long-lived Colitogenic CD4+ Memory T Cells Residing Outside the Intestine Participate in the Perpetuation of Chronic Colitis. (2009)
  • 著者名/発表者名: Nemoto Y, Sakamoto N, et al
  • 雑誌名: J Immunol 183 ページ: 5059-5068
  • 査読あり
• [雑誌論文] Adoptive immunotherapy with liver allograft-derived lymphocytes induces anti-HCV activity after liver transplantation in humans and humanized mice. (2009)
  • 著者名/発表者名: Ohira M, Sakamoto N, et al
  • 雑誌名: J Clin Invest 119 ページ: 3226-35
  • 査読あり
• [雑誌論文] Prospects for future therapy of hepatitis C virus infection. (2009)
  • 著者名/発表者名: Sakamoto N, Wu GY
  • 雑誌名: Future Virology 4 ページ: 453-462
  • 査読あり
• [雑誌論文] Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq. (2009)
  • 著者名/発表者名: Wang SY, Sakamoto N, et al
  • 雑誌名: Biochem Biophys Res Commun 385 ページ: 230-235
  • 査読あり
• [雑誌論文] The isomerase active site of cyclophilin A is critical for hepatitis C virus replication. (2009)
  • 著者名/発表者名: Chatterji U, Sakamoto N, et al
  • 雑誌名: J Biol Chem 284 ページ: 16998-17005
  • 査読あり
• [雑誌論文] RANK-RANKL signaling pathway is critically involved in the function of CD4+CD25+ regulatory T cells in chronic colitis. (2009)
  • 著者名/発表者名: Totsuka T, Sakamoto N, et al
  • 雑誌名: J Immunol. 182 ページ: 6079-6087
  • 査読あり
• [雑誌論文] New therapeutic approaches to hepatitis C virus. (2009)
  • 著者名/発表者名: Sakamoto N, Watanabe M.
  • 雑誌名: J Gastroenterol. 44 ページ: 643-649
  • NAID: 10025175879
  • 査読あり
• [雑誌論文] Inhibition of intracellular hepatitis C virus replication by nelfinavir and synergistic effect with interferon-alpha. (2009)
  • 著者名/発表者名: Toma S, Sakamoto N, et al
  • 雑誌名: Journal of Viral Hepatitis 16 ページ: 506-512
  • 査読あり
• [雑誌論文] Signaling pathway via TNFa/NFkB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis. (2009)
  • 著者名/発表者名: Onizawa M, Sakamoto N, et al
  • 雑誌名: Am J Physiol Gastrointest Liver Physiol 296
  • 査読あり
• [雑誌論文] A functional genomic screen identifies cellular cofactors of hepatitis C virus replication. (2009)
  • 著者名/発表者名: Tai AW, Sakamoto N, et al
  • 雑誌名: Cell Host Microbe. 5 ページ: 298-307
  • 査読あり
• [雑誌論文] (2009)
  • 著者名/発表者名: 坂本直哉、横田隆徳
  • 雑誌名: siRNAによるC型肝炎遺伝子治療.バイオ医薬品の開発技術とシーズ(シーエムシー出版) ページ: 246-251
• [雑誌論文] Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia
  • 著者名/発表者名: Yamashita A, Abdus K, Furuta A, Matsuda Y, Fujita O, Tani H, Fujita Y, Fujimoto Y, Ikeda M, Kato N, Sakamoto N, Maekawa S, Enomoto N, Nakakoshi M, Tsubuki M, Sekiguchi Y, Thuneda S, Akimitsu N, Noda N, Tanaka J, Moriishi K
  • 雑誌名: Marine Drugs 巻: (in press)
• [学会発表] A high-content screening assay using infectious fluorescence-tagged hepatitis C virus reveals candidates fo rsmall molecule inhibitors of viral entry (2011)
  • 著者名/発表者名: Kusano-Kitazume A, Sakamoto N, Okuno Y, Yamamoto M, Sekine-Osajima Y, Nakagawa M, Kakinuma S, Kiyohashi K, Nitta S, Murakawa M, Hagiwara M, Watanabe M
  • 学会等名: 62th. Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: San Francisco, CA.(Poster# 383)
  • 年月日: 2011-11-04
• [学会発表] ITPA gene variant protects against treatment-induced anemia and improves viral clearance by pegylated interferon-alfa and ribavirin therapy in chronic henatitis C patients (2011)
  • 著者名/発表者名: Sakamoto N, Nakagawa M, Azuma S, Watanabe M, et al.
  • 学会等名: 62th. Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: San Francisco
  • 年月日: 2011-11-04
• [学会発表] MMP-2 and MMP-14 derived from donor cells enhance therapeutic efficacy of liver cell transplantation in mice (2011)
  • 著者名/発表者名: Kakinuma S, Sakamoto N, Watanabe M, et al.
  • 学会等名: 62th. Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: San Francisco
  • 年月日: 2011-11-04
• [学会発表] A high-content screening assay using infectious fluorescence-tagged hepatitis C virus reveals candidates for small molecule inhibitors of viral entry (2011)
  • 著者名/発表者名: Kusano-Kitazume A, Sakamoto N, Nakagawa M, Watanabe M, et al.
  • 学会等名: 62th. Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: San Francisco
  • 年月日: 2011-11-04
• [学会発表] Loww of Wnt5A promotes biliary differentiation of murine hepatic stem/progenitor cells (2011)
  • 著者名/発表者名: Kiyohashi K, Sakamoto N, Watanabe M, et al.
  • 学会等名: 62th. Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: San Francisco
  • 年月日: 2011-11-04
• [学会発表] Antiviral effect of a novel interferon-inducible protein, IFI-27, against hepatitis C virus replication (2011)
  • 著者名/発表者名: Itsuil Y, Sakamoto N, Watanabe M, et al.
  • 学会等名: 62th. Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: San Francisco
  • 年月日: 2011-11-04
• [学会発表] IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis C virus genotype 2a/2b chimeric clones (2011)
  • 著者名/発表者名: Suda G, Sakamoto N, Nakagawa M, Azuma S, Watanabe M, et al.
  • 学会等名: 62th. Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: San Francisco
  • 年月日: 2011-11-04
• [学会発表] Prediction model of ribavirin-induced anemia incorporating ITPA genotype could identify chronic hepatitis C patients at high risk of relapse among virological responders to pegylated-interferon and ribavirin (2011)
  • 著者名/発表者名: Kurosaki M, Sakamoto N, et al.
  • 学会等名: 62th. Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: San Francisco
  • 年月日: 2011-11-04
• [学会発表] IL28B and ITPA gene variants correlate with treatment efficacy in pegylated-interferon plus ribavirin therapy for chronic hepatitis C (2011)
  • 著者名/発表者名: Matsuura K, Sakamoto N, et al.
  • 学会等名: 62th. Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: San Francisco
  • 年月日: 2011-11-04
• [学会発表] Mutations in the interferon sensitivity determining region of HCV, age and total ribavirin dose is an independent predictor of relapse among early virological responders to peg-interferon plus ribavirin therapy (2011)
  • 著者名/発表者名: Kurosaki M, Sakamoto N, Nakagawa M, et al.
  • 学会等名: 62th. Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: San Francisco
  • 年月日: 2011-11-04
• [学会発表] Development of an RNA polymerase I-driven adenoviral vector and its application in an HCV replication assay (2011)
  • 著者名/発表者名: Takeshi Yoshida, Fumi Satoh, Watari Akihiro, Masuo Kondoh, Hiroyuk iMizuguchi, Naoya Sakamoto, Kiyohito Yagi
  • 学会等名: 18th. International Meeting on Hepatitis C Virus & Related Viruses
  • 発表場所: Seattle, WA
  • 年月日: 2011-09-08
• [学会発表] Analysis of interferon signaling by infectious hepatitis C virus clones with substitutions of core amino acids 70 and 91 (2011)
  • 著者名/発表者名: Naoya Sakamoto, Yusuke Funaoka, Goki Suda, Mina Nakagawa, Sei Kakinuma, Mamoru Watanabe
  • 学会等名: 18th. International Meeting on Hepatitis C Virus & RelatedViruses
  • 発表場所: Seattle, WA
  • 年月日: 2011-09-08
• [学会発表] HCV-NS4B targets STING anda brogates RIG-I-mediated type-Iinterferon-dependent innate immune response (2011)
  • 著者名/発表者名: Sayuri Nitta, Naoya Sakamoto, Megumi Tasaka-Fujita, Kei Kiyohashi, Akiko Kusano-Kitazume, Miyako Murakawa, Kouhei Yoshino, Kako Mishima, SeiKakinuma, Mina Nakagawa, Mamoru Watanabe
  • 学会等名: 18th. International Meeting on Hepatitis C Virus & Related Viruses
  • 発表場所: Seattle, WA
  • 年月日: 2011-09-08
• [学会発表] Development of an RNA polymerase I-driven adenoviral vector and its application in an HCV replication assay (2011)
  • 著者名/発表者名: Yoshida T, Sakamoto N, et al.
  • 学会等名: 18th. International Meeting on Hepatitis C Virus & Related Viruses
  • 発表場所: Seattle
  • 年月日: 2011-09-08
• [学会発表] Analysis of interferon signaling by infectious hepatitis C virus clones with substitutions of core amino acids 70 and 91 (2011)
  • 著者名/発表者名: Sakamoto N, Nakagawa M, Watanabe M, et al.
  • 学会等名: 18th. International Meeting on Hepatitis C Virus & Related Viruses
  • 発表場所: Seattle
  • 年月日: 2011-09-08
• [学会発表] HCV-NS4B targets STING and abrogates RIG-I-mediated type-I interferon-dependent innate immune response (2011)
  • 著者名/発表者名: Nitta S, Sakamoto N, Nakagawa M, Watanabe M, et al.
  • 学会等名: 18th. International Meeting on Hepatitis C Virus & Related Viruses
  • 発表場所: Seattle
  • 年月日: 2011-09-08
• [学会発表] Development of RNA pol-driven adenovirus vector expressing hepatitis C virus replicon (2011)
  • 著者名/発表者名: Yoshiaki Yamagishi, Takeshi Yoshida, Masuo Kondoh, Hiroyuki Mizuguchi, Naoya Sakamoto, Akihiro Watari, Kiyohito Yagi
  • 学会等名: Experimental Biology 2011
  • 発表場所: Washington, DC
  • 年月日: 2011-04-13
• [学会発表] Development of RNA pol-driven adenovirus vector expressing hepatitis C virus replicon (2011)
  • 著者名/発表者名: Yamagishi Y, Sakamoto N, et al.
  • 学会等名: Experimental Biology 2011
  • 発表場所: Washington
  • 年月日: 2011-04-13
• [学会発表] タイトル:IL28B遺伝子多型と治療抵抗性ウイルス変異からみたC型慢性肝炎の治療抵抗メカニズムの解析(ワークショップ) (2010)
  • 著者名/発表者名: 中川美奈、柿沼晴、坂本直哉
  • 学会等名: 第38回日本肝臓学会東部会
  • 発表場所: 東京
  • 年月日: 2010-12-02
• [学会発表] ウイルスおよび宿主遺伝子情報に基づくC型慢性肝炎の治療戦略(パネルディスカッション) (2010)
  • 著者名/発表者名: 中川美奈、柿沼晴、坂本直哉
  • 学会等名: 第38回日本肝臓学会東部会
  • 発表場所: 東京
  • 年月日: 2010-12-02
• [学会発表] C型慢性肝炎のインターフェロン治療効果におけるインターロイキン-6(IL-6)の関与(パネルディスカッション) (2010)
  • 著者名/発表者名: 中川美奈、坂本直哉、渡辺守
  • 学会等名: JDDW2010(第14回日本肝臓学会大会)
  • 発表場所: 横浜
  • 年月日: 2010-10-14
• [学会発表] HCV増殖を制御する宿主インターフェロン誘導遣伝子GBP-1が介する分子機構(ワークショップ) (2010)
  • 著者名/発表者名: 井津井康浩、坂本直哉、渡辺守
  • 学会等名: JDDW20lO(第14回日本肝臓学会大会)
  • 発表場所: 横浜
  • 年月日: 2010-10-14
• [学会発表] Genotype 2b HCV感染培養系におけるIL6を介したInterferOn抵抗性発現機構の解析(ワークショップ) (2010)
  • 著者名/発表者名: 須田剛生、坂本直哉、渡辺守
  • 学会等名: JDDW2010(第14回日本肝臓学会大会)
  • 発表場所: 横浜
  • 年月日: 2010-10-14
• [学会発表] Identification of Novel Small Molecules Inhibitors of Hepatitis C Virus Replication Using a Cell-Based High-Throughput Screen (2010)
  • 著者名/発表者名: Akiko Kusano-Kitazume, Naoya Sakamoto, Yuko Sekine-Osajima, Seishin Azuma, Mina Nakagawa, Sei Kakinuma, Yuki Nishimura-Sakurai, Yukiko Okuno, Masatoshi Hagiwara, and Mamoru Watanabe
  • 学会等名: 17th. International Meeting on Hepatitis C Virus & Related Viruses
  • 発表場所: Yokohama, Japan
  • 年月日: 2010-09-09
• [学会発表] The inhibitory effect of triterpenoid compound with or without interferonαon Hepatitis C virus infection (2010)
  • 著者名/発表者名: Takako Watanabe, Naoya Sakamoto, Mina Nakagawa, Yasuhiro Itsui, Yuki Nishimura-Sakurai, Megumi Tasaka-Fujita, Yuko Sekine-Osajima, and Mamoru Watanabe
  • 学会等名: 17th. International Meeting on Hepatitis C Virus & Related Viruses
  • 発表場所: Yokohama, Japan
  • 年月日: 2010-09-09
• [学会発表] HCV genotype 2a/2b感染クローンを用いたInterferon抵抗性発現機構の解析(シンポジウム) (2010)
  • 著者名/発表者名: 坂本直哉、須田剛生、渡辺守
  • 学会等名: 第47回日本消化器免疫学会
  • 発表場所: 大津
  • 年月日: 2010-07-07
• [学会発表] ウイルス遺伝子および宿主IL28B遺伝子情報を統合したC型慢性肝炎治療のオーダーメイド化.(シンポジウム) (2010)
  • 著者名/発表者名: 坂本直哉、中川美奈、渡辺守
  • 学会等名: 第46回日本肝臓学会総会
  • 発表場所: 山形
  • 年月日: 2010-05-27
• [学会発表] SR蛋白リン酸化酵素(SRPK)阻害剤によるHCV増殖抑制効果の解析(ワークシヨップ) (2010)
  • 著者名/発表者名: 唐鎌優子、坂本直哉、小野木博、井津井康浩、中川美奈、柿沼晴、東正新、萩原正敏、渡辺守
  • 学会等名: 第46回日本肝臓学会総会
  • 発表場所: 山形
  • 年月日: 2010-05-27
• [学会発表] HCV増殖を制御するインターフェロン誘導性蛋白GBP-1が介する分子免疫機構(シンポジウム) (2010)
  • 著者名/発表者名: 井津井康浩、坂本直哉、渡辺守
  • 学会等名: 第96回日本消化器病学会総会
  • 発表場所: 新潟
  • 年月日: 2010-04-22
• [学会発表] In-vitro replication and interferon sensitivity of core aa 70 and 91 mutant HCV cell culture (2009)
  • 著者名/発表者名: Yusuke Funaoka, Naoya Sakamoto, Goki Suda, Yasuhiro Itsui, Mina Nakagawa, Kako Mishima, Yuko Karakama, Machi Yamamoto, Cheng-Hsin Chen-Azuma, Sei Kakinuma and Mamoru Watanabe
  • 学会等名: 60th. Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: Boston, MA
  • 年月日: 2009-10-30
• [学会発表] In-vitro and in-vivo Characterization of a new genotype 2b HCV clone and 2b/JFH1 intergenotypic chimera and analyses of the factor that regulate interferon sensitivity (2009)
  • 著者名/発表者名: Goki Suda, Naoya Sakamoto, Yasuhiro Itsui, Mina Nakagawa, Kako Mishima, Yuko Karakama, Machi Yamamoto, Cheng-Hsin Chen, Sei Kaki numa, KazuakiChayama, Michio Imamura and Mamoru Watanabe
  • 学会等名: 60th. Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: Boston, MA
  • 年月日: 2009-10-30
• [学会発表] In-vitro replication and interferon sensitivity of core aa 70 and 91 mutant HCV cell culture. (2009)
  • 著者名/発表者名: Funaoka Y, Sakamoto N, et al
  • 学会等名: 60th.Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: Boston
  • 年月日: 2009-10-30
• [学会発表] In-vitro and in-vivo Characterization of a new genotype 2b HCV clone and 2b/JFH1 intergenotypic chimera and analyses of the factor that regulate interferon sensitivity. (2009)
  • 著者名/発表者名: Suda G, Sakamoto N, et al
  • 学会等名: 60th.Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: Boston
  • 年月日: 2009-10-30
• [学会発表] Antiviral effects of interferon-induced proteins GBP-1 and its interactions with hepatitis C virus NS5B protein. (2009)
  • 著者名/発表者名: Itsui Y, Sakamoto N, et al
  • 学会等名: 60th.Annual Meeting of American Association for the Study of Liver Diseases
  • 発表場所: Boston
  • 年月日: 2009-10-30
• [学会発表] Establishment and genetic analyses of cytopathogenic HCV-JFH1 mutants by plaque-forming assay (2009)
  • 著者名/発表者名: Kako Mishima, Naoya Sakamoto, Yuko Sekine-Osajima, Mina Nakagawa, Megumi Tasaka, Yuki Nishimura-Sakurai, Yasuhiro Itsui, Takaji Wakita, and Mamoru Watanabe
  • 学会等名: 16th. International Meeting on Hepatitis C Virus & Related Viruses
  • 発表場所: Nice, France
  • 年月日: 2009-10-03
• [学会発表] Establishment and genetic analyses of cytopathogenic HCV-JFH1 mutants by plaque-forming assay. (2009)
  • 著者名/発表者名: Mishima K, Sakamoto N, et al
  • 学会等名: 16th.International Meeting on Hepatitis C Virus & Related Viruses
  • 発表場所: Nice
  • 年月日: 2009-10-03
• [図書] siRNAによるC型肝炎遺伝子治療.バイオ医薬品の開発技術とシーズ (2009)
  • 著者名/発表者名: 坂本直哉、横田隆〓
  • 出版者: シーエムシー出版
• [産業財産権] C型肝炎ウイルスの増殖を抑制する医薬組成物 (2011)
  • 発明者名: 坂本直哉、渡辺守、北詰晶子、萩原正敏、奥野友紀子
  • 権利者名: 東京医科歯科大学
  • 産業財産権番号: 2011-194082
  • 出願年月日: 2011-09-06