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

Abstract

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.

• Authors: Ning Li, Yanxu Zhang, Shuangxiu Wu, Ruodan Xu, Zhiqing Li, Jindong Zhu, Hongliang Wang, Xiao Li, Mingyao Tian, Huijun Lu, Ningyi Jin, Chengyu Jiang
• Journal: Science bulletin (Sci Bull (Beijing)) Vol. 64 Issue 3 Pg. 180-188 (Feb 15 2019) ISSN: 2095-9273 [Print] Netherlands
• PMID: 32288967 (Publication Type: Journal Article)
• Copyright: © 2018 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.