論文 - 詳細
| RRC ID | 81800 |
|---|---|
| 著者 | Ma Y, Nakamoto S, Ao J, Qiang N, Kogure T, Ogawa K, Nakagawa M, Fujiwara K, Iwanaga T, Kojima R, Kanzaki H, Koroki K, Kobayashi K, Kanogawa N, Kiyono S, Nakamura M, Kondo T, Nakagawa R, Ogasawara S, Muroyama R, Chiba T, Kato J, Kato N. |
| タイトル | Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus. |
| ジャーナル | Int J Mol Sci |
| Abstract |
A functional cure of hepatitis B virus (HBV) infection or HB antigen loss is rarely achieved by nucleos(t)ide analogs which target viral polymerase. HBx protein is a regulatory protein associated with HBV replication. We thought to identify antiviral compounds targeting HBx protein by analyzing HBx binding activity. Recombinant GST-tagged HBx protein was applied on an FDA-approved drug library chip including 1018 compounds to determine binding affinity by surface plasmon resonance imaging (SPRi) using a PlexArray HT system. GST protein alone was used for control experiments. Candidate compounds were tested for anti-HBV activity as well as cell viability using HepG2.2.15.7 cells and HBV-infected human hepatocytes. Of the 1018 compounds screened, 24 compounds showed binding to HBx protein. Of the top 6 compounds with high affinity to HBx protein, tranilast was found to inhibit HBV replication without affecting cell viability using HepG2.2.15.7 cells. Tranilast also inhibited HBV infection using cultured human hepatocytes. Tranilast reduced HB antigen level dose-dependently. Overall, theSPRi screening assay identified novel drug candidates targeting HBx protein. Tranilast and its related compounds warrant further investigation for the treatment of HBV infection. |
| 巻・号 | 23(19) |
| 公開日 | 2022-10-10 |
| DOI | 10.3390/ijms231912015 |
| PII | ijms231912015 |
| PMID | 36233317 |
| PMC | PMC9569680 |
| MeSH | Antiviral Agents / metabolism Antiviral Agents / pharmacology Hep G2 Cells Hepatitis B* Hepatitis B virus* Hepatocytes / metabolism Humans Viral Regulatory and Accessory Proteins / metabolism Virus Replication ortho-Aminobenzoates / pharmacology |
| IF | 4.556 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa Hep G2 |