Tauroursodeoxycholic acid (TUDCA) inhibits influenza A viral infection by disrupting viral proton channel M2

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Ning Li, Tsinghua University
  • ,
  • Yanxu Zhang, Tsinghua University
  • ,
  • Shuangxiu Wu, Tsinghua University
  • ,
  • Ruodan Xu
  • ,
  • Zhiqing Li, Tsinghua University
  • ,
  • Jindong Zhu, Tsinghua University
  • ,
  • Hongliang Wang, Tsinghua University
  • ,
  • Xiao Li, Academy of Military Medical Sciences
  • ,
  • Mingyao Tian, Academy of Military Medical Sciences
  • ,
  • Huijun Lu, Academy of Military Medical Sciences
  • ,
  • Ningyi Jin, Academy of Military Medical Sciences
  • ,
  • Chengyu Jiang, Tsinghua University

Influenza is a persistent threat to human health and there is a continuing requirement for updating anti-influenza strategies. Initiated by observations of different endoplasmic reticulum (ER) responses of host to seasonal H1N1 and highly pathogenic avian influenza (HPAI) A H5N1 infections, we identified an alternative antiviral role of tauroursodeoxycholic acid (TUDCA), a clinically available ER stress inhibitor, both in vitro and in vivo. Rather than modulating ER stress in host cells, TUDCA abolished the proton conductivity of viral M2 by disrupting its oligomeric states, which induces inefficient viral infection. We also showed that M2 penetrated cells, whose intracellular uptake depended on its proton channel activity, an effect observed in both TUDCA and M2 inhibitor amantadine. The identification and application of TUDCA as an inhibitor of M2 proton channel will expand our understanding of IAV biology and complement current anti-IAV arsenals.

Original languageEnglish
JournalScience Bulletin
Volume64
Issue3
Pages (from-to)180-188
Number of pages9
ISSN2095-9273
DOIs
Publication statusPublished - Feb 2019

    Research areas

  • Cell-penetrating peptide, Influenza, M2 proton channel, Oligomerization inhibitor, TUDCA, Virus entry, DRUG, PROTEIN, ENTRY, BILE-SALTS, CHOLESTEROL, MECHANISM, VIRUS M2, ER STRESS, ACUTE LUNG INJURY, M-2 ION-CHANNEL

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