ウイルス感染増殖系を基盤とした天然化合物新規生理機能の同定

2015 Fiscal Year Annual Research Report

• Project Area: Chemical Biology using bioactive natural products as specific ligands: identification of molecular targets and regulation of bioactivity
• Project/Area Number: 26102747
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: 渡士 幸一 国立感染症研究所, ウイルス第二部, 主任研究官 (40378948)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 天然物 / ウイルス / 肝炎ウイルス / 複製 / 侵入

Outline of Annual Research Achievements

真菌二次代謝産物由来天然化合物ライブラリーより、neoechinulin B (NeoB)がC型肝炎ウイルス(HCV)複製を抑制することを見出した。NeoBは細胞毒性をほとんど示すことなく用量依存的にHCV複製及びそれによる粒子作成を抑制した。またトランスクリプトーム解析及びレポーターアッセイより、NeoBは肝細胞内のliver X receptor (LXR)の転写活性を特異的に阻害することが明らかとなった。また誘導体解析より、この活性にはNeoB内のジケトピペラジン骨格が重要であることも示唆された。NeoBはLXRに直接相互作用することでその転写活性を阻害し、LXR下流遺伝子の発現調節を脱制御することで、肝細胞内脂質代謝等を修飾すると考えられた。neoechinulin BによりLXR活性を低下させたHCV感染細胞においては、HCV複製の場と考えられている二重膜ベシクル形成が大きく低下していることが観察された。以上のことより、本研究ではNeoBが新規LXRアンタゴニストであることが示唆された。またNeoBによるLXR不活性化はウイルス複製の場形成低下を介してHCV産生を減少させると考えられた。
一方本研究では同じライブラリーより、B型肝炎ウイルス(HBV)感染を低下させる新規三環系ポリケチドを同定し、これをvanitaracin Aと命名した。vanitaracin Aは細胞毒性を示すことなく用量依存的にHBV侵入を低下させ、その活性はIC50 = 0.61 uM, CC50 > 256 uMであった。生化学的アッセイ及び表面プラズモン共鳴により、vanitaracin AはHBV受容体であるNTCPに直接相互作用するリガンドであることを明らかにした。vanitaracin Aは様々な遺伝子型のHBV感染を阻害し、また同じくNTCP依存的に感染するD型肝炎ウイルス感染も阻害する一方で、NTCP非依存的なHCV感染にはほとんど影響を与えなかった。このようにvanitaracin Aは新たな抗HBV剤の有用なリード化合物になると期待される。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] INTS(フランス)
  • Country Name: FRANCE
  • Counterpart Institution: INTS
• [Int'l Joint Research] All India Institute of Medical Sciences/Transl Health Sci Tech Inst/Intl Center Gen Eng Biotechnol(インド)
  • Country Name: INDIA
  • Counterpart Institution: All India Institute of Medical Sciences/Transl Health Sci Tech Inst/Intl Center Gen Eng Biotechnol
  • # of Other Institutions: 2
• [Int'l Joint Research] Erasmus MC-University Medical Center(オランダ)
  • Country Name: NETHERLANDS
  • Counterpart Institution: Erasmus MC-University Medical Center
• [Journal Article] Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B (2016)
  • Author(s): Kong L, Fujimoto A, Nakamura M, Aoyagi H, Matsuda M, Watashi K, Suzuki R, Arita M, Yamagoe S, Dohmae N, Suzuki T, Sakamaki Y, Ichinose S, Suzuki T, Wakita T, Aizaki H
  • Journal Title: J Virol Volume: 90 Pages: 3093-3111
  • DOI: 10.1128/JVI.01540-15
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anti-hepatitis C Virus Natural Product from a Fungus, Penicillium herquei (2016)
  • Author(s): Nishikori S, Takemoto K, Kamisuki S, Nakajima S, Kuramochi K, Tsukuda S, Iwamoto M, Katayama Y, Suzuki T, Kobayashi S, Watashi K, Sugawara F
  • Journal Title: J Nat Prod Volume: 79 Pages: 442-446
  • DOI: 10.1021/acs.jnatprod.5b00555
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Single-domain intrabodies against hepatitis C virus core inhibit viral propagation and core-induced NFκB activation (2016)
  • Author(s): Suzuki R, Saito K, Matsuda M, Sato M, Kanegae Y, Shi G, Watashi K, Aizaki H, Chiba J, Saito I, Wakita T, Suzuki T
  • Journal Title: J Gen Virol Volume: 97 Pages: 887-892
  • DOI: 10.1099/jgv.0.000423
  • Peer Reviewed
• [Journal Article] Hepatocyte Factor JMJD5 Regulates Hepatitis B Virus Replication through Interaction with HBx (2016)
  • Author(s): Kouwaki T, Okamoto T, Ito A, Sugiyama Y, Yamashita K, Suzuki T, Kusakabe S, Hirano J, Fukuhara T, Yamashita A, Saito K, Okuzaki D, Watashi K, Sugiyama M, Yoshio S, Standley DM, Kanto T, Mizokami M, Moriishi K, Matsuura Y
  • Journal Title: J Virol Volume: 90 Pages: 3530-3542
  • DOI: 10.1128/JVI.02776-15
  • Peer Reviewed
• [Journal Article] Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals (2016)
  • Author(s): Sankhyan A, Sharma C, Dutta D, Sharma T, Chosdol K, Wakita T, Watashi K, Awasthi A, Acharya SK, Khanna N, Tiwari A, Sinha S
  • Journal Title: Sci Rep Volume: 6 Pages: 21240
  • DOI: 10.1038/srep21240
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] B型肝炎ウイルス研究の進歩 (2016)
  • Author(s): 渡士幸一、脇田隆字
  • Journal Title: Pharma Medica Volume: 34 Pages: 15-18
• [Journal Article] Novel robust in vitro hepatitis B virus infection model using fresh human hepatocytes isolated from humanized mice (2015)
  • Author(s): Ishida Y, Yamasaki C, Yanagi A, Yoshizane Y, Fujikawa K, Watashi K, Abe H, Wakita T, Hayes CN, Chayama K, Tateno C
  • Journal Title: Am J Pathol Volume: 185 Pages: 1275-1285
  • DOI: 10.1016/j.ajpath.2015.01.028
  • Peer Reviewed
• [Journal Article] Hepatitis B Virus and Hepatitis D Virus Entry, Species Specificity, and Tissue Tropism (2015)
  • Author(s): Watashi K, Wakita T
  • Journal Title: Cold Spring Harb Perspect Med Volume: 5 Pages: a021378
  • DOI: 10.1101/cshperspect.a021378
  • Peer Reviewed / Open Access
• [Journal Article] Isolation and structure of vanitaracin A, a novel anti-hepatitis B virus compound from Talaromyces sp (2015)
  • Author(s): Matsunaga H, Kamisuki S, Kaneko M, Yamaguchi Y, Takeuchi T, Watashi K, Sugawara F
  • Journal Title: Bioorg Med Chem Lett Volume: 25 Pages: 4325-4328
  • DOI: 10.1016/j.bmcl.2015.07.067
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Molecular dissection of HBV evasion from restriction factor tetherin: A new perspective for antiviral cell therapy (2015)
  • Author(s): Miyakawa K, Matsunaga S, Watashi K, Sugiyama M, Kimura H, Yamamoto N, Mizokami M, Wakita T, Ryo A
  • Journal Title: Oncotarget Volume: 6 Pages: 21840-21852
  • Peer Reviewed
• [Journal Article] Amino Acid Polymorphisms in Hepatitis C Virus Core Affect Infectious Virus Production and Major Histocompatibility Complex Class I Molecule Expression (2015)
  • Author(s): Tasaka-Fujita M, Sugiyama N, Kang W, Masaki T, Murayama A, Yamada N, Sugiyama R, Tsukuda S, Watashi K, Asahina Y, Sakamoto N, Wakita T, Shin EC, Kato T
  • Journal Title: Sci Rep Volume: 5 Pages: 13994
  • DOI: 10.1038/srep13994
  • Peer Reviewed / Open Access
• [Journal Article] A Novel Tricyclic Polyketide, Vanitaracin A, Specifically Inhibits the Entry of Hepatitis B and D Viruses by Targeting Sodium Taurocholate Cotransporting Polypeptide (2015)
  • Author(s): Kaneko M, Watashi K, Kamisuki S, Matsunaga H, Iwamoto M, Kawai F, Ohashi H, Tsukuda S, Shimura S, Suzuki R, Aizaki H, Sugiyama M, Park SY, Ito T, Ohtani N, Sugawara F, Tanaka Y, Mizokami M, Sureau C, Wakita T
  • Journal Title: J Virol Volume: 89 Pages: 11945-11953
  • DOI: 10.1128/JVI.01855-15
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of Antiviral Agents Targeting Hepatitis B Virus Promoter from Extracts of Indonesian Marine Organisms by a Novel Cell-Based Screening Assay (2015)
  • Author(s): Yamashita A, Fujimoto Y, Tamaki M, Setiawan A, Tanaka T, Okuyama-Dobashi K, Kasai H, Watashi K, Wakita T, Toyama M, Baba M, de Voogd NJ, Maekawa S, Enomoto N, Tanaka J, Moriishi K
  • Journal Title: Mar Drugs Volume: 13 Pages: 6759-6773
  • DOI: 10.3390/md13116759
  • Peer Reviewed / Open Access
• [Journal Article] Hepatitis B virus efficiently infects non-adherent hepatoma cells via human sodium taurocholate cotransporting polypeptide (2015)
  • Author(s): Okuyama-Dobashi K, Kasai H, Tanaka T, Yamashita A, Yasumoto J, Chen W, Okamoto T, Maekawa S, Watashi K, Wakita T, Ryo A, Suzuki T, Matsuura Y, Enomoto N, Moriishi K
  • Journal Title: Sci Rep Volume: 5 Pages: 17047
  • DOI: 10.1038/srep17047
  • Peer Reviewed / Open Access
• [Journal Article] Disparity of basal and therapeutically activated interferon signalling in constraining hepatitis E virus infection (2015)
  • Author(s): Zhou X, Xu L, Wang W, Watashi K, Wang Y, Sprengers D, de Ruiter PE, van der Laan LJ, Metselaar HJ, Kamar N, Peppelenbosch MP, Pan Q
  • Journal Title: J Viral Hepat Volume: 23 Pages: 294-304
  • DOI: 10.1111/jvh.12491
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 新規B型肝炎抗ウイルス薬開発の現状 (2015)
  • Author(s): 渡士幸一、脇田隆字
  • Journal Title: カレントテラピー Volume: 33 Pages: 903-907
• [Journal Article] HBVの細胞内侵入機構とこれを標的とした創薬 (2015)
  • Author(s): 渡士幸一
  • Journal Title: 日本臨床 Volume: 73増刊号9 Pages: 372-376
• [Journal Article] B型肝炎ウイルスエントリーについて：メカニズムとその阻害 (2015)
  • Author(s): 渡士幸一、脇田隆字
  • Journal Title: 肝胆膵 Volume: 71 Pages: 1053-1058
• [Presentation] Hepatitis C virus cell culture system identifies fungi-derived NeoB as a liver X receptor inhibitor (2015)
  • Author(s): Watashi K
  • Organizer: Pacifichem 2015
  • Place of Presentation: Honolulu
  • Year and Date: 2015-12-16 – 2015-12-16
  • Int'l Joint Research
• [Presentation] 海綿由来セキステルペン系化合物metachromin AのB型肝炎ウイルスコアプロモーター抑制活性を介した抗ウイルス活性 (2015)
  • Author(s): 山下篤哉, 田中智久, 土橋香織, 葛西宏威, 渡士幸一, 脇田隆字, 外山正明, 馬場昌範, 前川伸哉, 榎本信幸, 玉城麻友美, 田中淳一, 森石恆司
  • Organizer: BMB 2015
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-02 – 2015-12-02
• [Presentation] Development of a novel vaccine platform based on Japanese encephalitis viruses (2015)
  • Author(s): Suzuki R, Saga R, Fujimoto A, Watanabe N, Matsuda M, Hasegawa M, Watashi K, Aizaki H, Nakamura N, Konishi E, Kato T, Tajima S, Takasaki T, Takeyama H, Wakita T
  • Organizer: BMB 2015
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-02 – 2015-12-02
• [Presentation] Development ofa cell culture and infection system for hepatitis B virus using 3D cultured non-neoplasmic HuS-E/2 cells (2015)
  • Author(s): Akahori Y, Kato H, Fujita T, Moriishi K, Watashi K, Wakita T, Hijikata M
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Transfer hepatitis C virus from human liver cells to hepatic stellate cells (2015)
  • Author(s): Zaitsu T, Aoyagi H, Fujimoto A, Matsuda M, Watanabe N, Watashi K, Suzuki R, Fukuhara T, Matsuura Y, Sakamaki Y, Ichinose S, Wake K, Suzuki T, Iijima H, Matsuura T, Tamura K, Wakita T, Aizaki H
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Identification of flavonoid derivative that directly acts on hepatitis B virus surface protein and inhibits viral entry (2015)
  • Author(s): Tsukuda S, Watashi K, Hamada Y, Isogawa M, Iwamoto M, Suzuki R, Aizaki H, Kojima S, Sugiyama M, Saito A, Tanaka Y, Mizokami M, Wakita T
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Investigation of mechanisms of interaction between host glycosylation system and hepatitis B virus replication system (2015)
  • Author(s): Okutsu S, Ito K, Yoneda M, Angata K, Watashi K, Wakita T, Iijima S, Tanaka Y, Tong S, Mizokami M, Narimatsu H
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicit neutralizing antibodies against JEV and hepatitis C virus (2015)
  • Author(s): Saga R, Fujimoto A, Watanabe N, Matsuda M, Hasegawa M, Watashi K, Aizaki H, Nakamura N, Konishi E, Kato T, Tajima S, Takasaki T, Takeyama H, Wakita T, Suzuki R
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Identification of novel pyrimidotriazinone derivatives as inhibitors of HBV replication (2015)
  • Author(s): Toyama M, Hamasaki T, Okamoto M, Watashi K, Wakita T, Baba M
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] A new fungi-derived vanitaracin A specifically inhibits the entry of hepatitis B and D viruses through interacting with NTCP (2015)
  • Author(s): Kaneko M, Watashi K, Kamisuki S, Matsunaga H, Iwamoto M, Kawai F, Ohashi H, Tsukuda S, Shimura S, Suzuki R, Aizaki H, Sugiyama M, Park Sy, Ohtani N, Sugawara F, Tanaka Y, Mizokami M, Wakita T
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Multimerization of hepatitis B virus core protein regulated by microtubules (2015)
  • Author(s): Iwamoto M, Watashi K, Sugiyama M, Suzuki R, Aizaki H, Tanaka Y, Mizokami M, Ohtani N, Koiwai O, Wakita T
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Surfeit 4 is involved in HCV replication by interacting with NS4B (2015)
  • Author(s): Kong L, Aoyagi H, Matsuda M, Fujimoto A, Watashi K, Suzuki R, Yamagoe S, Dohmae N, Suzuki T, Sakamaki Y, Ichinose S, Suzuki T, Wakita T, Aizaki H
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Hepatitis B virus downregulates expression of CIDE-B and CIDE-C and impairs lipid droplet growth (2015)
  • Author(s): Yasumoto J, Kasai H, Tanaka T, Watashi K, Wakita T, Yamashita A, Dobashi-Okuyama K, Moriishi K
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] SKIV2L-mediated RNA-exosome regulation of HBV replication (2015)
  • Author(s): Aly HH, Watashi K, Chayama K, Kato T, Wakita T
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Egression of hepatitis B virus particles is promoted by long chain saturated fatty acid (2015)
  • Author(s): Okamura H, Akahori Y, Kim S, Nio Y, Watashi K, Wakita T, Hijikata M
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Flutamide-mediated disruption of lipid droplets impairs the host permisiveness to hepatitis C virus production (2015)
  • Author(s): Ohashi H, Watashi K, Nakajima S, Kim S, Suzuki R, Aizaki H, Fukasawa M, Kamisuki S, Sugawara F, Ohtani N, Wakita T
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Human iPS-derived hepatocytes as an in vitro HBV infection model (2015)
  • Author(s): Sakurai F, Yamamoto T, Mitani S, Takayama K, Tachibana M, Watashi K, Wakita T, Iijima S, Tanaka Y, Mizuguchi H
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Metachromin A, sesquiterpene from marine sponge Dactylospongia metachromia, exerts anti-HBV activity via inhibition of HBV core promoter (2015)
  • Author(s): Yamashita A, Tanaka T, Okuyama-Dobashi K, Kasai H, Watashi K, Wakita T, Toyama M, Baba M, Moriishi K
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23 – 2015-11-23
• [Presentation] Chemical genetics for virus research: Interface of drug development and basic virology (2015)
  • Author(s): Watashi K
  • Organizer: The 63rd Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-22 – 2015-11-22
  • Invited
• [Presentation] Japanese encephalitis virus (JEV)-subviral particles harboring HCV neutralization epitopes elicit neutralizing antibodies against JEV and HCV (2015)
  • Author(s): Saga R, Fujimoto A, Watanabe N, Matsuda M, Hasegawa M, Watashi K, Aizaki H, Nakamura N, Konishi E, Kato T, Takeyama H, Wakita T, Suzuki R
  • Organizer: 22nd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Strasbourg (France)
  • Year and Date: 2015-10-11 – 2015-10-11
  • Int'l Joint Research
• [Presentation] Quantifying activity optimizes drug combinations against hepatitis C virus infection (2015)
  • Author(s): Iwami S, Tanaka Y, Wakita T, Watashi K
  • Organizer: 22nd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Strasbourg (France)
  • Year and Date: 2015-10-11 – 2015-10-11
  • Int'l Joint Research
• [Presentation] Development of a cell culture and infection system for hepatitis B virus using 3D cultured immortalized human hepatocytes (2015)
  • Author(s): Akahori Y, Kato H, Fujita T, Moriishi K, Watashi K, Wakita T, Hijikata M
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] Cilnidipine inhibits the early phase of HBV infection in a NTCP-independent mechanism (2015)
  • Author(s): Tsukuda S, Watashi K, Iwamoto M, Suzuki R, Aizaki H, Kojima S, Tanaka Y, Wakita T
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] Identification of HBV entry inhibitors, based on the cyclosporin structure (2015)
  • Author(s): Shimura S, Watashi K, Sluder A, Peel M, Kawai F, Sugiyama M, Park SY, Tanaka Y, Mizokami M, Wakita T
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] Dual function of RIG-I as innate antiviral mediator against hepatitis B virus (2015)
  • Author(s): Sato S, Li K, Kameyama T, Hayashi T, Ishida Y, Murakami S, Watanabe T, Iijima S, Sakurai Y, Watashi K, Tsutsumi S, Sato Y, Akita H, Wakita T, Rice Cm, Harashima H, Kohara M, Tanaka Y, Takaoka A
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] Anti-HBV talens delivered by recombinant adeno-associated viral vectors (rAAV) efficiently inhibit HBV replication in vivo and in vitro (2015)
  • Author(s): Nicholson S, Moyo B, Bloom K, Mussolino C, Cathomen T, Watashi K, Ely A, Arbuthnot P
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] Development of anti-HBs monoclonal antibody targeting HBs-NTCP interaction (2015)
  • Author(s): Matsunaga S, Miyakawa K, Watashi K, Sugiyama M, Mizokami M, Wakita T, Ryo A
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] Pyrimidotriazinone derivatives as novel inhibitors of hepatitis B virus core assembly (2015)
  • Author(s): Toyama M, Hamasaki T, Okamoto M, Watashi K, Wakita T, Baba M
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] Identification of a new tricyclic polyketide, vanitaracin A, which inhibits the entry of HBV, HDV, and nucleoside analog-resistant HBV though targeting NTCP (2015)
  • Author(s): Kaneko M, Watashi K, Kamisuki S, Matsunaga H, Iwamoto M, Kawai F, Ohashi H, Tsukuda S, Shimura S, Suzuki R, Aizaki H, Sugiyama M, Park SY, Ohtani N, Sugawara F, Tanaka Y, Mizokami M, Sureau C, Wakita T
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] Inhibition of hepatitis B virus infection by docosahexaenoic acid in cultured cells (2015)
  • Author(s): Fukasawa M, Shimizu Y, Shirasago Y, Watashi K, Tanaka Y, Wakita T, Kondoh M, Yagi K, Hanada K
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] Identification of NTCP-targeting small molecules that inhibit HBV entry by cell-based and in vitro technologies (2015)
  • Author(s): Watashi K, Tsukuda S, Shimura S, Kaneko M, Sluder A, Peel M, Kamisuki S, Matsunaga S, Morishita R, Futamura Y, Kondoh Y, Suzuki R, Aizaki H, Sugiyama M, Borroto-Esoda K, Ryo A, Sugawara F, Osada H, Tanaka Y, Mizokami M, Wakita T
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] Molecular dissection of HBV evasion from restriction factor tetherin (2015)
  • Author(s): Miyakawa K, Matsunaga S, Watashi K, Sugiyama M, Mizokami M, Wakita T, Ryo A
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] Investigation of the mechanism of interaction between host glycosylation system and hepatitis B virus replication system (2015)
  • Author(s): Ito K, Yoneda M, Angata K, Watashi K, Wakita T, Iijima S, Tanaka Y, Tong S, Kuno A, Sugiyama M, Mizokami M, Narimatsu H
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] SKIV2L-dependent HBV-RNA degradation by the RNA-exosome, a new anti-HBV host mechanism (2015)
  • Author(s): Aly HH, Watashi K, Chayama K, Kato T, Wakita T
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] Long chain saturated fatty acid contributes to efficient egression of hepatitis B virus particles (2015)
  • Author(s): Okamura H, Akahori Y, Kim S, Nio Y, Watashi K, Wakita T, Hijikata M
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] AAV-delivered engineered repressor transcription activator-like effectors (rTALEs) inactivate hepatitis B virus replication in hNTCP cells and in mice (2015)
  • Author(s): Moyo B, Nicholson S, Roelofse I, Bloom K, Mussolino C, Cathomen T, Watashi K, Ely A, Arbuthnot P
  • Organizer: 2015 International Meeting of Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim(Germany)
  • Year and Date: 2015-10-07 – 2015-10-07
  • Int'l Joint Research
• [Presentation] C型肝炎治療薬の個性を探る ～多剤併用から費用対効果の考察まで～ (2015)
  • Author(s): 渡士幸一
  • Organizer: ウイルス感染現象における宿主細胞コンピテンシーの分子基盤 第2回若手研究会
  • Place of Presentation: 三浦
  • Year and Date: 2015-07-18 – 2015-07-18
• [Presentation] 創薬を指向した肝炎ウイルス感染増殖機構の解析 (2015)
  • Author(s): 渡士幸一
  • Organizer: 京都大学ウイルス研究所 ウイルス研究の潮流
  • Place of Presentation: 京都
  • Year and Date: 2015-07-15 – 2015-07-15
  • Invited
• [Presentation] NTCPを標的としたB型肝炎ウイルス感染阻害戦略 (2015)
  • Author(s): 渡士幸一
  • Organizer: 第31回日本DDS学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-02 – 2015-07-02
  • Invited
• [Presentation] ウイルス感染増殖系を基盤とした天然化合物の新規生理機能の解析 (2015)
  • Author(s): 渡士幸一
  • Organizer: 天然物ケミカルバイオロジー 分子標的と活性制御 第7回公開シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2015-06-08 – 2015-06-08
• [Presentation] 新規真菌二次代謝産物 SF177 の B 型肝炎ウイルス感染阻害活性および NTCP トランスポーター阻害活性の同定 (2015)
  • Author(s): 金子学, 渡士幸一, 松永大輝, 紙透伸治, 岩本将士, 河合文啓, 鈴木亮介, 相崎英樹, 朴三用, 菅原二三男, 脇田隆字
  • Organizer: 第25回抗ウイルス療法学会総会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-23 – 2015-05-23
• [Presentation] B型肝炎ウイルスに対する直接標的薬proanthocyanidinおよび宿主標的薬vanitaracinの同定および感染阻害機構の解析 (2015)
  • Author(s): 渡士幸一, 九十田千子, 金子学, 松永大輝, 紙透伸治, 齊藤安貴子, 鈴木亮介, 相崎英樹, 杉山真也, 溝上雅史, 菅原二三男, 田中靖人, 脇田隆字
  • Organizer: 第25回抗ウイルス療法学会総会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-23 – 2015-05-23
• [Presentation] Neoechinulin Bのliver X receptor転写阻害効果の同定およびそれによるC型肝炎ウイルス複製制御機構の解析 (2015)
  • Author(s): 渡士幸一, 中嶋翔, 紙透伸治, Izaguirre-Carbonell J, Kwon Atj, 鈴木治和, 九十田千子, 岡田麻衣子, 鈴木亮介, 相崎英樹, 菅原二三男, 脇田隆字
  • Organizer: 第25回抗ウイルス療法学会総会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-23 – 2015-05-23
• [Presentation] カイメン由来化合物metachromin A及びその類縁化合物の抗HBV活性の検討 (2015)
  • Author(s): 山下篤哉, 田中智久, 葛西宏威, 渡士幸一, 脇田隆字, 外山政明, 馬場昌範, 前川伸哉, 榎本信幸, 玉城麻友美, 田中淳一, 森石恆司
  • Organizer: 第25回抗ウイルス療法学会総会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-23 – 2015-05-23
• [Presentation] 新規核酸誘導体7-deazaneplanocin A誘導体の抗HBV効果について (2015)
  • Author(s): 外山政明, 濱崎隆之, 岡本実佳, 渡士幸一, 脇田隆字, Ashoke Sharon, 馬場昌範
  • Organizer: 第25回抗ウイルス療法学会総会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-23 – 2015-05-23
• [Presentation] B型肝炎ウイルスの感染に対するRIG-Iを介した自然免疫応答機構 (2015)
  • Author(s): 佐藤精一, 李凱, 亀山武志, 林隆也, 石田雄二, 村上周子, 渡邊綱正, 飯島沙幸, 櫻井遊, 渡士幸一, 堤進, 佐藤悠介, 秋田英万, 脇田隆字, Rice Cm, 原島秀吉, 小原道法, 田中靖人, 高岡晃教
  • Organizer: 第25回抗ウイルス療法学会総会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-23 – 2015-05-23
• [Presentation] ヒト肝癌細胞 FLC4 における B 型肝炎ウイルスレセプター NTCP の発現と誘導に関する検討 (2015)
  • Author(s): 松浦知和, 松本喜弘, 永森収志, 渡士幸一, 金井好克, 小嶋聡一, 脇田隆字, 相崎英樹
  • Organizer: 第51回日本肝臓学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2015-05-22 – 2015-05-22
• [Presentation] NTCP as a drug target of anti-hepatitis B virus infection (2015)
  • Author(s): Watashi K
  • Organizer: 2015 American Association of Pharmaceutical Scientists (AAPS)/ International Transporter Consortium (ITC) Workshop on Drug Transporter in ADME: From the Bench to the Bedside
  • Place of Presentation: Baltimore (USA)
  • Year and Date: 2015-04-21 – 2015-04-21
  • Int'l Joint Research / Invited