Mechanistic analysis of hepatitis C virus life cycle using small molecules
Project/Area Number |
23790514
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Virology
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Research Institution | National Institute of Infectious Diseases |
Principal Investigator |
WATASHI Koichi 国立感染症研究所, ウイルス第二部, 主任研究官 (40378948)
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Project Period (FY) |
2011 – 2012
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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Keywords | HCV / PLD / 抗ウイルス / ウイルス / phospholipase / 肝炎 |
Research Abstract |
We analyzed the anti-hepatitis C virus (HCV) mechanism of halopemide, which was identified to reduce HCV production by a cell-based chemical screening. Halopemide inhibited the secretion process of HCV. Its anti-HCV effect was mediated by host phospholipase D (PLD). PLD regulated the release of HCV but not host secreted proteins. Inhibition of PLD stalled HCV particles around the Golgi. The above data suggest that host PLD specifically mediates the post-Golgi trafficking of HCV, and halopemide inhibited this process to reduce the production of infectious HCV.
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Report
(4 results)
Research Products
(107 results)
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[Journal Article] Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter NTCP2014
Author(s)
Watashi K, Sluder A, Daito T, Matsunaga S, Ryo A, Nagamori S, Iwamoto M, Nakajima S, Tsukuda S, Borroto-Esoda K, Sugiyama M, Tanaka Y, Kanai Y, Kusuhara H, Mizokami M, Wakita T.
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Journal Title
Hepatology
Volume: 59
Pages: 1726-1737
Related Report
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[Journal Article] Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP2014
Author(s)
Iwamoto M, Watashi K, Tsukuda S, Aly HH, Fukasawa M, Fujimoto A, Suzuki R, Aizaki H, Ito T, Koiwai O, Kusuhara H, Wakita T.
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Journal Title
Biochem Biophys Res Commun
Volume: 443
Pages: 808-813
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[Journal Article] Total Synthesis and Anti-Hepatitis C Virus Activity of MA0262013
Author(s)
Shimura S, Ishima M, Nakajima S, Fujii T, Himeno N, Ikeda K, Izaguirre-Carbonell J, Murata H, Takeuchi T, Kamisuki S, Suzuki T, Kuramochi K, Watashi K, Kobayashi S, Sugawara F
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Journal Title
J Am Chem Soc
Volume: 135
Pages: 18949-18956
Related Report
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[Journal Article] Interleukin-1 and tumor necrosis factor-αtrigger restriction of hepatitis B virus infection via a cytidine deaminase activation-induced cytidine deaminase (AID)2013
Author(s)
Watashi K, Liang G, Iwamoto M, Marusawa H, Uchida N, Daito T, Kitamura K, Muramatsu M, Ohashi H, Kiyohara T, Suzuki R, Li J, Tong S, Tanaka Y, Murata K, Aizaki H, Wakita T.
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Journal Title
J Biol Chem
Volume: 288
Pages: 31715-31727
NAID
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[Journal Article] Antiviral activity of glycyrrhizin against hepatitis C virus in vitro2013
Author(s)
Matsumoto Y, Matsuura T, Aoyagi H, Matsuda M, Hmwe SS, Date T, Watanabe N, Watashi K, Suzuki R, Ichinose S, Wake K, Suzuki T, Miyamura T, Wakita T, Aizaki H
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Journal Title
Related Report
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[Journal Article] Total synthesis and anti-hepatitis C virus activity of MA0262013
Author(s)
Shimura S, Ishima M, Nakajima S, Fujii T, Himeno N, Ikeda K, Izaguirre-Carbonell J, Murata H, Takeuchi T, Kamisuki S, Suzuki T, Kuramochi K, Watashi K, Kobayashi S, Sugawara F
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Journal Title
J Am Chem Soc
Volume: 135
Issue: 50
Pages: 18949-18956
DOI
Related Report
Peer Reviewed
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[Journal Article] Interleukin-1 and tumor necrosis factor-α trigger restriction of hepatitis B virus infection via a cytidine deaminase activation-induced cytidine deaminase (AID)2013
Author(s)
Watashi K, Liang G, Iwamoto M, Marusawa H, Uchida N, Daito T, Kitamura K, Muramatsu M, Ohashi H, Kiyohara T, Suzuki R, Li J, Tong S, Tanaka Y, Murata K, Aizaki H, Wakita T
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Journal Title
J Biol Chem
Volume: 288
Issue: 44
Pages: 31715-31727
DOI
NAID
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Peer Reviewed
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[Journal Article] Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B2011
Author(s)
Morohashi K+, Sahara H, Watashi K+, Iwabata K, Sunoki T, Kuramochi K, Takakusagi K, Miyashita H, Sato N, Tanabe A, Shimotohno K, Kobayashi S, Sakaguchi K, Sugawara F. (+equally contributed)
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[Presentation] Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting sodium taurocholate cotransporting polypeptide2013
Author(s)
K. Watashi, A. Sluder, S. Matsunaga, Ryo, S. Nakajima, M. Iwamoto, S. Tsukuda, K. Borroto-Esoda, M. Sugiyama, Y. Tanaka, M. Mizokami, T. Wakita
Organizer
2013 International Meeting on Molecular Biology of Hepatitis B viruses
Place of Presentation
Shanghai(China)
Related Report
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[Presentation] Interleukin-1 and tumor necrosis factor-alpha trigger restriction of hepatitis B virus infection via a cytidine deaminase AID2013
Author(s)
K. Watashi, G. Liang, M. Iwamoto, H. Marusawa, K. Kitamura, M. Muramatsu, R. Suzuki, J. Li, S. Tong, Y. Tanaka, K. Murata, H. Aizaki, T. Wakita
Organizer
2013 International Meeting on Molecular Biology of Hepatitis B viruses
Place of Presentation
Shanghai(China)
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[Presentation] Synthetic studies of MA026, a novel antiviral lipocyclodepsipeptide2012
Author(s)
S. Shimura, M. Ishima, I. Ota, E. Tsutsui, S. kamisuki, H. Murata, T. Yamazaki, T. Suzuki, K. Kuramochi, T. Takeuchi, K. Watashi, S. Kobayashi, F. Sugawara
Organizer
International Congress on Natural Products Research 2012
Place of Presentation
New York(USA)
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[Presentation] Synthetic studies of MA026, a novel antiviral lipocyclodepsipeptide2012
Author(s)
S. Shimura, M. Ishima, I. Ota, E. Tsutsui, S. kamisuki, H. Murata, T. Yamazaki, T. Suzuki, K. Kuramochi, T. Takeuchi, K. Watashi, S. Kobayashi, F. Sugawara
Organizer
International Congress on Natural Products Research 2012
Place of Presentation
New York (USA)
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[Presentation] Identification of a novel cellular RNA helicase-like protein as a target for cyclosporin A that is involved in hepatitis C virus genome replication2011
Author(s)
K. Watashi, H. Sahara, K. Morohashi, K. Iwabata, T. Sunoki, K. Kuramochi, K. Takakusagi, H. Miyashita, N. Sato, A. Tanabe, K. Shimotohno, S. Kobayashi, K. Sakaguchi, F. Sugawara
Organizer
18th International Symposium on hepatitis C virus and related viruses
Place of Presentation
Seattle, USA
Related Report
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[Presentation] Identification of lipid droplet-associated membrane proteins that are involved in HCV production2011
Author(s)
H. Aizaki, Y. Matsumoto, K. Goto, K. Watashi, R. Suzuki, M. Fukasawa, K. Hanada, S. Sato, N. Takahashi, Y. Matsuura, K. Motojima, T. Miyamura, T. Suzuki, T. Wakita
Organizer
18th International Symposium on hepatitis C virus and related viruses
Place of Presentation
Seattle, USA
Related Report
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[Presentation] Identification of novel NS5A-associated proteins in the host-cell membrane fraction and their International Symposium on hepatitis C virus and related viruses2011
Author(s)
K. Goto, T. Kimura, K. Watashi, R. Suzuki, S. Yamagoe, T. Miyamura, K. Moriya, H. Yotsuyanagi, K. Koike, T. Suzuki, T. Wakita, H. Aizaki
Organizer
18th International Symposium on hepatitis C virus and related viruses
Place of Presentation
Seattle, USA
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[Presentation] Identification of novel NS5A-associated proteins in the host-cell membrane fraction and their role in HCV life cycle2011
Author(s)
Goto K, Kimura T, Watashi K, Suzuki R, Yamagoe S, Miyamura T, Moriya K, Yotsuyanagi H, Koike K, Suzuki T, Wakita T, Aizaki H
Organizer
18th International Symposium on hepatitis C virus and related viruses
Place of Presentation
Seattle, USA
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