Search for new classes of HCV therapeutics by large scale screening of antiviral compounds and host cellular factors

通过大规模筛选抗病毒化合物和宿主细胞因子寻找新的 HCV 疗法

• 批准号: 19390196
• 负责人: SAKAMOTO Naoya
• 金额: $ 11.98万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2008
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19390196/
• 关键词: HCVレプリコン; HCV-JFH1培養系; HVC-JFH1培養系

当該研究期間において我々は、HCV感染・増殖細胞モデルを用いて薬剤・生理活性化合物・短鎖ペプチドの抗ウイルス作用の網羅的スクリーニング、および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) HCV-Feo replicon細胞を用いてDiversity-OrientedSynthesis(DOS)法で合成した8,000種の化合物のスクリーニングを施行し、HCV増殖を抑制する41種の化合物を同定し、構造活性相関解析にIC50の優れた5個のepoxide誘導体を同定した。(2) HCV複製増殖に関与する代謝・シグナルネットワークの網羅的解析により、脂質・コレステロール代謝に関わる代謝・シグナルネットワークの関与、関連薬剤の効果を確認した。(3) 漢方生薬成分化合物の細胞内HCV増殖に対する効果をHCVレプリコンシステムを用いて解析を行い、甘草由来の2種の化合物、isoliquiritigenin、及びglycycoumarinにHCV増殖抑制作用を見出した。今後これらの知見を統合し、HCV感染サイクルにおけるウイルスおよび宿主蛋白相互作用の細胞・分子レベルでの理解を深め、新規クラス抗HCV療法薬剤の開発・実用化に必要な基盤情報の蓄積を到達目標とし引き続き研究を遂行する。本研究で同定された化合物の作用機構の解析、小動物モデルを用いた効果・安全性の検証を進めることにより新たな抗ウイルス薬剤の開発につながると思われる。

During the period of this study, when we were infected with HCV, we used the physiologically active compounds to short-term the anti-immune effect of the host factor of the anti-immune network, and we successfully explored the host factor of HCV colonization. The main results are as follows: (1) the HCV-Feo replicon cell was synthesized by Diversity-OrientedSynthesis (DOS) method. The compounds were synthesized by the method of Diversity-OrientedSynthesis (DOS), the compounds were synthesized by the method of DNA Diversity-OrientedSynthesis (DOS), the compounds were synthesized by the method of DNA Diversity-OrientedSynthesis (DOS), the compounds were synthesized by the method of DNA Diversity-OrientedSynthesis (DOS), and the compounds were identified by the inhibition of HCV colonization. (2) HCV replication and reproducibility. This is not true for the resolution of the Internet. No, no. (3) Intracelluar HCV colonization, HCV colonization, HCV colonization inhibition, Glycyrrhiza uralensis Fisch, Glycyrrhiza uralensis Fisch, isoliquiritigenin, and Glycyrrhiza uralensis. In the future, we have been informed that the HCV infection has caused significant changes in the host protein interaction, and that the cellular molecules have a good understanding of the host protein interaction, and that the new anti-HCV method has been developed and the necessary information has been accumulated for the purpose of conducting the study. The purpose of this study is to determine the mechanism of the action of compounds, and to improve the safety and safety of small chemicals.

项目成果

Potential relevance of cytoplasmic viral sensors and related regulators involving innate immunity in antiviral response

• DOI: 10.1053/j.gastro.2008.02.019
• 发表时间: 2008-05-01
• 期刊: GASTROENTEROLOGY
• 影响因子: 29.4
• 作者: Asahina, Yasuhiro;Izumi, Namiki;Miyake, Shozo
• 通讯作者: Miyake, Shozo

Two flavonoids extracts from a herb, Glycyrrhizae radix, inhibit in-vitro hepatitis C virus replication

甘草中的两种黄酮类提取物可抑制体外丙型肝炎病毒复制

• 发表时间: 2009
• 期刊: Hepatology Res 39
• 作者: Sekine-Osajima Y;Nakagawa M;et al
• 通讯作者: et al

Proteasomal degradation of Atoh1 by aberrant Wnt signaling maintains the undifferentiated state of colon cancer

• DOI: 10.1016/j.bbrc.2008.02.011
• 发表时间: 2008-04-18
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Aragaki, Mikayo;Tsuchiya, Kiichiro;Watanabe, Mamoru
• 通讯作者: Watanabe, Mamoru

Synergistic inhibition of intracellular hepatitis C virus replication by nelfinavir and interferon-a.

奈非那韦和干扰素-a 协同抑制细胞内丙型肝炎病毒复制。

• 发表时间: 2009
• 期刊: Journal of Viral Hepatitis In press
• 作者: Satoshi Toma;Tsuyoshi Yamashiro;Shingo Arakaki;Joji Shiroma;Tatsuji Maeshiro;Kenji Hibiya;Naoya Sakamoto;Fukunori Kinjo;Masao Tateyama;Jiro Fujita
• 通讯作者: Jiro Fujita

Griseofulvin, an oral antifungal agent, suppresses HCV replication in vitro.

灰黄霉素是一种口服抗真菌剂，可在体外抑制 HCV 复制。

• 发表时间: 2008
• 期刊: Hepatol. Res. (In press)
• 作者: Jin H;Maekawa S;et. al.
• 通讯作者: et. al.