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Targeting virus-interacting host ion channels as a novel antiviral strategy

Acta Pharmacologica Sinica (2025)Cite this article

Abstract

Ion channels are transmembrane protein complexes that control ion transport across the membranes and play a pivotal role for maintaining cellular homeostasis as well as in virus–host interactions. As obligate parasites, viruses hijack the host’s ion channel network with spatiotemporal precision to drive their life cycle. In this review, we summarize the key function of ion channels in this dynamic interplay. We then delve into the ways by which different ion channel types facilitate discrete stages of viral infection, including entry, genome release, replication, assembly, and release. By examining dynamic changes in ion channel activity during infection, we reveal how viruses manipulate host ion channels to regulate their life cycle. Moreover, the clinical potential of targeting host ion channels as an innovative antiviral strategy is highlighted. The objective of this review is to comprehensively elucidate host ion channel-virus interactions, as well as the potential of existing ion channel modulators as antiviral drugs, laying the theoretical foundation for the development of novel antiviral therapies.

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Fig. 1: Viruses exploit host ion channels to facilitate entry.
Fig. 2: Ion channel activity significantly affects viral replication and release.
Fig. 3: Host ion channel activity is suppressed during the viral life cycle.

Data availability

No data were used for the research described in the article.

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Funding

This work was supported by grants from the National Key Research and Development Program of China (2024YFA1306500 to JY, 2023YFF1204000 to JY), the National Natural Science Foundation of China (32370761 to CX, 32171147 to JY, and 32371200 to JY), the Fundamental Research Funds for the Central Universities (2042022dx0003 to JY), and the State Key Laboratory for Animal Disease Control and Prevention (SKLADCPKFKT202515 to YYG).

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Authors and Affiliations

  1. State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, 430072, China

    Yu-yao Guo, Xiao-yi Mo, Jia-jing Wu, Chang Xie & Jing Yao

  2. State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China

    Yu-yao Guo

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  1. Yu-yao Guo
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  2. Xiao-yi Mo
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  3. Jia-jing Wu
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  4. Chang Xie
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  5. Jing Yao
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Contributions

YYG: Writing-original draft, Formal analysis, Data curation. XYM: Visualization, Formal analysis. JJW: Writing-original draft, Data curation. CX: Supervision, Visualization, Project administration. JY: Supervision, Visualization, Project administration.

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Correspondence to Chang Xie or Jing Yao.

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Guo, Yy., Mo, Xy., Wu, Jj. et al. Targeting virus-interacting host ion channels as a novel antiviral strategy. Acta Pharmacol Sin (2025). https://doi.org/10.1038/s41401-025-01677-6

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