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-Structure paper
| タイトル | Aglycone Polyether Ionophores Affecting Actin Filaments as Broad-Spectrum Antiviral Agents. |
|---|---|
| ジャーナル・号・ページ | ACS Pharmacol Transl Sci, Vol. 8, Issue 7, Page 2018-2032, Year 2025 |
| 掲載日 | 2025年7月11日 |
著者 | Minjian Huang / Jiaqi Li / Jing Li / Ben Hu / Ran Liu / Lianghao Huang / Caiqian Wang / Rong Hua / Chuanjian Wu / Zhuli Li / Zherui Zhang / Yanan Zhang / Yingjun Wu / Qiuyan Zhang / Yong Wang / Jing Liu / Zixin Deng / Wei Wang / Wei Hou / Ling Zhao / Yucheng Xia / Xiaolian Zhang / Longfei Wang / Bo Zhang / Tiangang Liu / ![]() |
| PubMed 要旨 | RNA viruses have high mutation rates and constitute an increasing global risk. As the viral target approach to develop antiviral drugs is inadequate for responding to an increasing diversity of ...RNA viruses have high mutation rates and constitute an increasing global risk. As the viral target approach to develop antiviral drugs is inadequate for responding to an increasing diversity of viruses, an urgent need exists for the development of new antivirals to prevent future outbreaks. Here, we show that aglycone ionophores maduramycin (Mad) and endusamycin (End) from are broadly virucidal against cytoplasmic replicated viruses, including Japanese encephalitis virus (JEV), rabies virus, hepatitis C virus, vesicular stomatitis virus, hantavirus, dengue virus, Zika virus, chikungunya virus, and SARS-CoV-2 in vitro. Mechanistic studies suggest Mad and End can target actin filaments and displace the DNase-I-binding loop (D-loop) into an outward conformation for stabilizing actin filaments and primarily inhibit viral replication. Liposome-encapsulated Mad or End fully protects mice against JEV infection in vivo. Thus, our results may provide potential and naturally produced antivirals to prevent the spread of viruses in animals. |
リンク | ACS Pharmacol Transl Sci / PubMed:40672661 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.44 - 2.45 Å |
| 構造データ | EMDB-38280, PDB-8xdl: EMDB-38281, PDB-8xdm: |
| 化合物 | ![]() ChemComp-ADP: ![]() ChemComp-MG: |
| 由来 |
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キーワード | PROTEIN BINDING / aglycone polyether ionophores / anti-tumor |
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