Search for new potential drug targets for Hepatitis B virus genome replication based on chemical biology

• Project/Area Number: 15K08507
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: YAMASAKI Manabu 公益財団法人微生物化学研究会, 微生物化学研究所, 研究員 (50442570)
• Co-Investigator(Renkei-kenkyūsha): SAITO Izumu 公益財団法人微生物化学研究会, 微生物化学研究所, チームリーダー (70158913) ; KANEGAE Yumi 東京慈恵会医科大学, 医学部, 准教授 (80251453) ; KONDO Saki 東京大学, 医科学研究所, 助教 (80451871) ; IGARASHI Masayuki 公益財団法人微生物化学研究会, 微生物化学研究所, 部長 (40260137) ; SAWA Ryuichi 公益財団法人微生物化学研究会, 微生物化学研究所, 上席室長 (50235454)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: B型肝炎ウイルス / 抗ウイルス薬 / ゲノム複製 / 創薬標的分子 / ケミカルバイオロジー

Outline of Final Research Achievements

There is a need for novel drug targets for treatment of chronic Hepatitis B virus (HBV) infection to expand our therapeutic repertoire. In this study, we screened in-house compound library and microbial fermentation broths using adenovirus-mediated efficient virus genome replication system, and performed mode-of-action studies using hit compounds for identification of new potential drug targets. In the course of our screening program, we identified three selective inhibitors, and found that the compound among them has a potential activity to exert host anti-HBV responses in addition to direct antiviral activity.

Research Products

• [Journal Article] Current landscape and future prospects of antiviral drugs derived from microbial products (2017)
  • Author(s): Takizawa Naoki、Yamasaki Manabu
  • Journal Title: The Journal of Antibiotics Volume: 71 Issue: 1 Pages: 45-52
  • DOI: 10.1038/ja.2017.115
  • Peer Reviewed
• [Journal Article] Efficient genome replication of hepatitis B virus using adenovirus vector: a compact pregenomic RNA-expression unit (2017)
  • Author(s): Suzuki M, Kondo S, Yamasaki M, Matsuda N, Nomoto A, Suzuki T, Saito I, Kanegae Y.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 41851-41851
  • DOI: 10.1038/srep41851
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Identification of an anti-HBV agent targeting viral genome replication using adenovirus vector (2017)
  • Author(s): 山﨑学、松田法恵、鈴木まりこ、鐘ヶ江裕美、斎藤泉、柴﨑正勝
  • Organizer: 第65回日本ウイルス学会学術集会
• [Presentation] Screening of a compound library for HBV inhibitors using adenovirus-mediated virus genome replication system (2015)
  • Author(s): 山﨑学、松田法恵、近藤小貴、鈴木まりこ、鐘ヶ江裕美、斎藤泉、野本明男、柴﨑正勝
  • Organizer: 第63回日本ウイルス学会学術総会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2015-11-22
• [Presentation] Efficient production of the replicating HBV genome using adenovirus vector (2015)
  • Author(s): 近藤小貴、鈴木まりこ、山﨑学、柴崎正勝、斎藤泉、鐘ヶ江裕美
  • Organizer: 第63回日本ウイルス学会学術総会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2015-11-22
• [Remarks]