Search and characterization of new helicase inhibitors and others from coral reef organisms

2012 Fiscal Year Final Research Report

• Project/Area Number: 22603007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: ケミカルバイオロジー
• Research Institution: University of the Ryukyus
• Principal Investigator: TANAKA Junichi 琉球大学, 理学部, 教授 (20163529)
• Co-Investigator(Renkei-kenkyūsha): NODA Naohiro 産業技術総合研究所, バイオメディカル研究部門, 主任研究員 (70415727) ; ANNO Kumiko 広島大学, 薬学部, 助教 (30452585)
• Project Period (FY): 2010 – 2012
• Keywords: C 型肝炎ウイルス / NS3 ヘリケース / サンゴ礁生物 / 海綿 / ウミシダ

Research Abstract

To discover lead molecules against hepatitis C virus, we screened extracts of coral reef organisms with PET assay targeting NS3 helicase and with replicon assay utilizing cultured hepatocarcinoma cells transfected with virus-like genes. Hit extracts were subjected to chemical characterization to identify or determine the bioactive molecules. In addition, we examined the mode of action of the hit molecules.

Research Products

• [Journal Article] Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia (2012)
  • Author(s): Yamashita, A.; Salam, K.A.; 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.; Tsuneda, S.; Akimitsu, N.; Noda, N.; Tanaka, J.; Moriishi, K
  • Journal Title: Marine Drugs Volume: 10 Pages: 744-761
  • DOI: DOI:10.3390/md10040744
  • Peer Reviewed
• [Journal Article] Inhibition of both protease and helicase activities of hepatitis C virus NS3 by an ethyl acetate extract of marine sponge Amphimedon sp (2012)
  • Author(s): Fujimoto, Y.; Salam, K.A.; Furuta, A.; Matsuda, Y.; Fujita, O.; Tani, H.; Ikeda, M.; Kato, N.; Sakamoto, N.; Maekawa, S.; Enomoto, N.; de Voogd, N. J.; Nakakoshi, M.; Tsubuki, M.; Sekiguchi, Y.; Tsuneda, S.; Akimitsu, N.; Noda, N.; Yamashita, A.; Tanaka, J.; Moriishi, K
  • Journal Title: PLoS ONE Volume: 7 Pages: e48685
  • DOI: DOI:10.1371/journal.pone.0048685
  • Peer Reviewed
• [Journal Article] Inhibition of hepatitis C virus NS3 helicase by manoalide (2012)
  • Author(s): Salam, K.A.; Noda, N.; Furuta, A.; Tsuneda, S.; Sekiguchi, Y.; Yamashita, A.; Moriishi, K.; Nakakoshi, M.; Tsubuki, M.; Tani, H.; Tanaka, J.Akimitsu, N.
  • Journal Title: J. Nat. Prod Volume: 75 Pages: 650-654
  • DOI: DOI:10.1021/np200883s
  • Peer Reviewed
• [Journal Article] Real-time monitoring of RNA helicase activity using fluorescence resonance energy transfer in vitro (2010)
  • Author(s): Tani, H.; Fujita, O.; Furuta, A.; Matsuda, Y.; Miyata, R.; Akimitsu, N.; Tanaka, J.; Tsuneda, S.; Sekiguchi, Y.; Noda, N.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 393 Pages: 131-136
  • DOI: DOI:10.1016/j.bbrc.2010.01.100
  • Peer Reviewed
• [Journal Article] Inhibition of hepatitis C virus NS3 helicase by cholesterol sulfate without inhibition of ATPase and RNA binding
  • Author(s): Yamashita, A.; Moriishi, K.; Tsubuki, M.; Nakakoshi, M.; Sekiguchi, Y.; Tsuneda, S.; Noda, N
  • Journal Title: J. Enz. Inhib. Med. Chem
  • DOI: DOI:10.3109/14756366.2013.766607
  • Peer Reviewed
• [Journal Article] Psammaplin A inhibits hepatitis C virus NS3 helicase
  • Author(s): Salam, K.A.; Furuta, A.; Noda, N.; Tsuneda, S.; Sekiguchi, Y.; Yamashita, A.; Moriishi, K.; Nakakoshi, M.; Tsubuki, M.; Tani, H.; Tanaka, J.; Akimitsu, N
  • Journal Title: J. Nat. Med. in press
  • DOI: DOI:10.1007/s11418-013-0742-7
  • Peer Reviewed
• [Presentation] 海洋生物抽出物より取得した複数種の硫酸化合物による C 型肝炎ウイルス NS3 helicase 阻害作用 (2012)
  • Author(s): 古田篤史 他
  • Organizer: 海洋生物抽出物より取得した複数種の硫酸化合物による C 型肝炎ウイルス NS3 helicase 阻害作用
  • Place of Presentation: 神戸国際会議場.
  • Year and Date: 2012-10-25
• [Presentation] Identification of novel hepatitis C virus NS3 inhibitors: psammaplin A and halisulfate 3 (2012)
  • Author(s): Salam, K.A.
  • Organizer: Japan-China Medical Workshop 2012 on DrugDiscoveries and Therapeutics - New Perspectives in Cancer Prevention
  • Place of Presentation: 東京大学
  • Year and Date: 2012-10-22
• [Presentation] Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia (2012)
  • Author(s): Yamashita, A
  • Organizer: 25th International Conference on Antiviral Research
  • Place of Presentation: Hotel Royton - Sapporo.
  • Year and Date: 2012-04-18
• [Presentation] Search for inhibitors against HCV NS3 helicase and chemical and genetic diversity of Sarcophyton soft corals (2011)
  • Author(s): Tanaka, J
  • Organizer: VIIth US-Japan Seminar on Marine Natural Products: Cross-disciplinary Expansions in Marine Bioorganic Chemistry
  • Place of Presentation: 沖縄コンベンションセンター
  • Year and Date: 2011-12-12
• [Presentation] 沖縄産ウミシダAlloeocomatella polycladia 抽出物の抗HCV NS3 helicase阻害作用によるHCV増殖抑制効果 (2011)
  • Author(s): 山下篤哉 他
  • Organizer: 第58回日本ウイルス学会
  • Place of Presentation: 徳島県郷土文化会館
  • Year and Date: 2011-11-07
• [Presentation] 海洋生物抽出物より取得したcholesterol sulfate による C 型肝炎ウイルス NS3 helicase 阻害作用 (2011)
  • Author(s): 古田篤史他
  • Organizer: 第63回日本生物工学会大会
  • Place of Presentation: 東京農工大学.
  • Year and Date: 2011-09-27
• [Presentation] Inhibitors against NS3 helicase of hepatitis C virus from coral reef invertebrates (2011)
  • Author(s): Tanaka, J
  • Organizer: 2011 American Society of Pharmacognosy Meeting
  • Place of Presentation: Paradise Point Resort, San Diego, USA
  • Year and Date: 2011-07-03
• [Presentation] Identification and biochemical characterization of novel hepatitis C virus NS3 inhibitors (2011)
  • Author(s): Salam, K.A
  • Organizer: manoalide and psammaplin A
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2011-06-16
• [Presentation] 海洋生物をライブラリーソースとした HCV NS3 Helicase 活性阻害化合物の探索 (2011)
  • Author(s): 山下篤哉他
  • Organizer: 第21回抗ウイルス療法研究会
  • Place of Presentation: 金沢市文化ホール
  • Year and Date: 2011-05-29