WEKO3
アイテム
HCV感染マウスを用いたNS5A, NS3またはNS5B阻害剤併用療法のgenotype間での抗ウイルス効果の検討
https://hiroshima.repo.nii.ac.jp/records/2005025
https://hiroshima.repo.nii.ac.jp/records/2005025ed21ba93-9399-4835-9e2c-b5cd85c947c8
| 名前 / ファイル | ライセンス | アクション |
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k6243_3.pdf (1.1 MB)
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k6243_1.pdf (170.9 KB)
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k6243_2.pdf (139.8 KB)
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| Item type | デフォルトアイテムタイプ_（フル）(1) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 公開日 | 2023-03-18 | |||||||||
| タイトル | ||||||||||
| タイトル | Combination therapy with NS5A, NS3 and NS5B inhibitors on different genotype of hepatitis C virus in human hepatocyte chimeric mice. | |||||||||
| 言語 | en | |||||||||
| タイトル | ||||||||||
| タイトル | HCV感染マウスを用いたNS5A, NS3またはNS5B阻害剤併用療法のgenotype間での抗ウイルス効果の検討 | |||||||||
| 言語 | ja | |||||||||
| 作成者 |
時, 牛
× 時, 牛
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| アクセス権 | ||||||||||
| アクセス権 | open access | |||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
| 主題 | ||||||||||
| 主題Scheme | NDC | |||||||||
| 主題 | 490 | |||||||||
| 内容記述 | ||||||||||
| 内容記述 | Objective: We recently demonstrated that combination treatment with NS3 protease and NS5B polymerase inhibitors succeeded in eradicating the virus in genotype 1b hepatitis C virus (HCV)-infected mice. In this study, we investigated the effect of combining an NS5A replication complex inhibitor (RCI) with either NS3 protease or NS5B inhibitors on elimination of HCV genotypes 1b, 2a and 2b. Design: The effects of Bristol-Myers Squibb (BMS)-605339 (NS3 protease inhibitor; PI), BMS-788329 (NS5ARCI) and BMS-821095 (NS5B non-nucleoside analogue inhibitor) on HCV genotypes 1b and 2a were examined using subgenomic HCV replicon cells. HCV genotype 1b, 2a or 2b-infected human hepatocyte chimeric mice were also treated with BMS-605339, BMS-788329 or BMS-821095 alone or in combination with two of the drugs for 4 weeks. Genotypic analysis of viral sequences was achieved by direct and ultra-deep sequencing. Results: Anti-HCV effects of BMS-605339 and BMS-821095 were more potent against genotype 1b than against genotype 2a. In in-vivo experiments, viral breakthrough due to the development of a high prevalence of drug-resistant variants was observed in mice treated with BMS-605339, BMS-788329 and BMS-821095 in monotherapy. In contrast to monotherapy, 4 weeks of combination therapy with the NS5A RCI and either NS3 PI or NS5B inhibitor succeeded in completely eradicating the virus in genotype 1b HCV-infected mice. Conversely, these combination therapies failed to eradicate the virus in mice infected with HCV genotypes 2a or 2b. Conclusions: These oral combination therapies may serve as a Peg-alfa-free treatment for patients chronically infected with HCV genotype 1b. | |||||||||
| 言語 | en | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| 資源タイプ | ||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||
| 資源タイプ | doctoral thesis | |||||||||
| 出版タイプ | ||||||||||
| 出版タイプ | NA | |||||||||
| 出版タイプResource | http://purl.org/coar/version/c_be7fb7dd8ff6fe43 | |||||||||
| 関連情報 | ||||||||||
| 関連タイプ | references | |||||||||
| 関連名称 | Niu Shi, Nobuhiko Hiraga, Michio Imamura, C Nelson Hayes, Yizhou Zhang, Keiichi Kosaka, Akihito Okazaki, Eisuke Murakami, Masataka Tsuge, Hiromi Abe, Hiroshi Aikata, Shoichi Takahashi, Hidenori Ochi, Chise Tateno-Mukaidani, Katsutoshi Yoshizato, Hirotaka Matsui, Akinori Kanai, Toshiya Inaba, Fiona McPhee, Min Gao, Kazuaki Chayama; Combination therapies with NS5A, NS3 and NS5B inhibitors on different genotypes of hepatitis C virus in human hepatocyte chimeric mice; Gut 2013;62:1055-1061. (doi: 10.1136/gutjnl-2012-302600) | |||||||||
| 関連情報 | ||||||||||
| 関連タイプ | references | |||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | http://doi.org/10.1136/gutjnl-2012-302600 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲第6243号 | |||||||||
| 学位名 | ||||||||||
| 言語 | ja | |||||||||
| 学位名 | 博士(医学) | |||||||||
| 学位名 | ||||||||||
| 言語 | en | |||||||||
| 学位名 | Philosophy in Medical Science | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2013-09-25 | |||||||||
| 学位授与機関 | ||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||
| 学位授与機関識別子 | 15401 | |||||||||
| 言語 | ja | |||||||||
| 学位授与機関名 | 広島大学 | |||||||||
| 学位授与機関 | ||||||||||
| 言語 | en | |||||||||
| 学位授与機関名 | Hiroshima University | |||||||||
| 旧ID | 40611 | |||||||||
