Aglycone Polyether Ionophores Affecting Actin Filaments as Broad-Spectrum Antiviral Agents
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 <i>Streptomyces</i> 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.
Authors
- Minjian Huang (ORCID: https://orcid.org/0009-0005-8622-0147)
- Lianghao Huang (ORCID: https://orcid.org/0000-0003-3494-5224)
- Rong-Hong Hua (ORCID: https://orcid.org/0000-0001-7034-5766)
- Tiangang Liu (ORCID: https://orcid.org/0000-0001-8087-0345)
- Ben Hu (ORCID: https://orcid.org/0000-0001-5451-1736)
- Zhu-Li Li (ORCID: https://orcid.org/0009-0009-4297-1001)
- Ling Zhao (ORCID: https://orcid.org/0000-0002-6644-2886)
- Xiao‐Lian Zhang (ORCID: https://orcid.org/0000-0002-8283-9381)
- Zherui Zhang (ORCID: https://orcid.org/0009-0000-3385-6161)
- Longfei Wang
- Caiqian Wang
- Chuanjian Wu
- Jing Li (ORCID: https://orcid.org/0009-0003-2593-829X)
- Jiaqi Li (ORCID: https://orcid.org/0000-0003-3831-6994)
- Bo Zhang (ORCID: https://orcid.org/0000-0001-8065-1273)
- Jing Liu (ORCID: https://orcid.org/0000-0003-1600-7744)
- Wei Qiang Wang (ORCID: https://orcid.org/0000-0002-1430-1360)
- Yong Wang (ORCID: https://orcid.org/0000-0003-4048-206X)
- Ran Liu (ORCID: https://orcid.org/0000-0002-9605-231X)
- Zixin Deng (ORCID: https://orcid.org/0000-0003-0724-3390)
- Yanan Zhang (ORCID: https://orcid.org/0000-0001-8472-1136)
- Yingjun Wu (ORCID: https://orcid.org/0000-0001-6567-7838)
- Qiu-Yan Zhang
- Wei Hou
- Yucheng Xia
Institutions
- Guilford Technical Community College (US)
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Sciences (CN)
- Huazhong Agricultural University (CN)
- Wuhan University (CN)
- Precision Therapeutics (United States) (US)
- Wuhan Institute of Virology (CN)
- Zhongnan Hospital of Wuhan University (CN)
- University of Chinese Academy of Sciences (CN)
- State Key Laboratory of Agricultural Microbiology
- Ocean University of China (CN)
Publication Details
- Journal
- ACS Pharmacology & Translational Science
- Published
- 2025-06-24
- DOI
- https://doi.org/10.1021/acsptsci.5c00144
- Primary Topic
- Viral Infections and Immunology Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Science and Technology Department of Hubei Province
- National Key Research and Development Program of China