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SRPKIN-1 as an inhibitor against hepatitis B virus blocking the viral particle formation and the early step of the viral infection
http://hdl.handle.net/10271/0002000253
http://hdl.handle.net/10271/00020002536b1b07af-544a-46c4-b539-046d71a8b3a5
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (1 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2024-12-20 | |||||||
| タイトル | ||||||||
| タイトル | SRPKIN-1 as an inhibitor against hepatitis B virus blocking the viral particle formation and the early step of the viral infection | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題 | Hepatitis B virus | |||||||
| キーワード | ||||||||
| 主題 | HBc | |||||||
| キーワード | ||||||||
| 主題 | Antiviral | |||||||
| キーワード | ||||||||
| 主題 | SRPK inhibitor | |||||||
| キーワード | ||||||||
| 主題 | Phosphorylation | |||||||
| 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 | |||||||
| 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 | |||||||
| その他のタイトル | ||||||||
| その他のタイトル | SRPKIN-1はB型肝炎ウイルス粒子形成と感染早期過程を阻害する | |||||||
| 著者 |
Li, Xiaofang
× Li, Xiaofang
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| 書誌情報 |
en : Antiviral Research 巻 220, p. 105756, ページ数 13 |
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| 出版者 | ||||||||
| 出版者 | Elsevier | |||||||
| 言語 | en | |||||||
| 権利 | ||||||||
| 言語 | en | |||||||
| 権利情報 | (C) 2023 The Authors. | |||||||
| 権利 | ||||||||
| 言語 | en | |||||||
| 権利情報 | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | New antiviral agents are needed for the treatment of hepatitis B virus (HBV) infection because currently available drugs do not completely eradicate chronic HBV in patients. Phosphorylation dynamics of the HBV core protein (HBc) regulate several processes in the HBV life cycle, including nucleocapsid formation, cell trafficking, and virus uncoating after entry. In this study, the SRPK inhibitors SPHINX31, SRPIN340, and SRPKIN-1 showed concentration-dependent anti-HBV activity. Detailed analysis of the effects of SRPKIN-1, which exhibited the strongest inhibitory activity, on the HBV replication process showed that it inhibits the formation of infectious particles by inhibiting pregenomic RNA packaging into capsids and nucleocapsid envelopment. Mass spectrometry analysis combined with cell-free translation system experiments revealed that hyperphosphorylation of the Cterminal domain of HBc is inhibited by SRPKIN-1. Further, SRPKIN-1 exhibited concentration-dependent inhibition of HBV infection not only in HepG2-hNTCP-C4 cells but also in fresh human hepatocytes (PXB cells) and in the single-round infection system. Treatment with SRPKIN-1 at the time of infection reduced the nuclease sensitivity of HBV DNA in the nuclear fraction. These results suggest that SRPKIN-1 has the potential to not only inhibit the HBV particle formation process but also impair the early stages of viral infection. | |||||||
| 言語 | en | |||||||
| 学位名 | ||||||||
| 学位名 | 博士（医学） | |||||||
| 学位の区分 | ||||||||
| 内容記述 | doctoral | |||||||
| 学位の分野 | ||||||||
| 内容記述 | 医学系研究科 | |||||||
| 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 | 13802 | |||||||
| 学位授与機関名 | 浜松医科大学 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2024-01-19 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第962号 | |||||||
| ISSN | ||||||||
| 収録物識別子タイプ | PISSN | |||||||
| 収録物識別子 | 0166-3542 | |||||||
| EISSN | ||||||||
| 収録物識別子タイプ | EISSN | |||||||
| 収録物識別子 | 1872-9096 | |||||||
| NII書誌ID | ||||||||
| 収録物識別子タイプ | NCID | |||||||
| 収録物識別子 | AA10623661 | |||||||
| PubMed番号 | ||||||||
| 関連タイプ | isIdenticalTo | |||||||
| 識別子タイプ | PMID | |||||||
| 関連識別子 | 37992764 | |||||||
| 出版社DOI | ||||||||
| 関連タイプ | isIdenticalTo | |||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | https://doi.org/10.1016/j.antiviral.2023.105756 | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | P | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_fa2ee174bc00049f | |||||||
