8XDM

F-actin-MAD

8XDM の概要

• エントリーDOI: 10.2210/pdb8xdm/pdb
• EMDBエントリー: 38281
• 分子名称: Actin, alpha skeletal muscle, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: aglycone polyether ionophores, anti-tumor, protein binding
• 由来する生物種: Oryctolagus cuniculus (rabbit)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 127684.44

構造登録者

Wang, L.,Li, J.,Liu, T.,Huang, M. (登録日: 2023-12-11, 公開日: 2024-12-18, 最終更新日: 2025-12-31)

主引用文献

Huang, M.,Li, J.,Li, J.,Hu, B.,Liu, R.,Huang, L.,Wang, C.,Hua, R.,Wu, C.,Li, Z.,Zhang, Z.,Zhang, Y.,Wu, Y.,Zhang, Q.,Wang, Y.,Liu, J.,Deng, Z.,Wang, W.,Hou, W.,Zhao, L.,Xia, Y.,Zhang, X.,Wang, L.,Zhang, B.,Liu, T.
Aglycone Polyether Ionophores Affecting Actin Filaments as Broad-Spectrum Antiviral Agents.
Acs Pharmacol Transl Sci, 8:2018-2032, 2025

PubMed Abstract: 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.

PubMed: 40672661
DOI: 10.1021/acsptsci.5c00144

実験手法

ELECTRON MICROSCOPY (2.45 Å)