8XDL

F-actin-END

Summary for 8XDL

• Entry DOI: 10.2210/pdb8xdl/pdb
• EMDB information: 38280
• Descriptor: Actin, alpha skeletal muscle, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION (3 entities in total)
• Functional Keywords: aglycone polyether ionophores, anti-tumor, protein binding
• Biological source: Oryctolagus cuniculus (rabbit)
• Total number of polymer chains: 3
• Total formula weight: 127684.44

Authors

Wang, L.,Li, J.,Liu, T.,Huang, M. (deposition date: 2023-12-11, release date: 2024-12-18, Last modification date: 2025-12-31)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.44 Å)