The modulation of metabolomics and antioxidant stress is involved in the effect of nitazoxanide against influenza A virus in vitro

IF 1.1 4区医学 Q4 VIROLOGY

Acta virologica Pub Date : 2023-06-23 DOI:10.3389/av.2023.11612

Zhen Huang, Haihong Zheng, Yanping Wang, Xiao-yang Wang, Chunmei Wang, Yingchun Liu, Wen Zhou, Zhaoxiong Wang, Ke‐Zhi Zhang

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引用次数: 1

Abstract

The prevalence of highly infectious influenza A virus (IAV) is still a major threat to global human health. Nitazoxanide (NTZ) possesses potent antiviral properties against the influenza virus. However, the role of small molecular metabolites and antioxidant stress in the NTZ’s anti-influenza virus mechanism is not yet fully understood. This study compared the changes in cellular metabolism, ROS levels, antioxidant enzyme activities, and Keap-1/Nrf2 pathway in IAV-infected MDCK cells after NTZ treatment in vitro, using LC-MS-based metabolomics, flow cytometry, immunoblot. We observed that the NTZ treatment in the IAV-infected cells drastically altered the metabolism of small molecules, among which eleven metabolites were highly relevant to NTZ. The virus induced oxidative stress was also remarkably suppressed by NTZ. Meanwhile, the Nrf2 pathway and some proteins with modulating antiviral activity were activated after NTZ treatment, protecting cells from IAV injury. Therefore, regulation of the intracellular oxidative state is the primary outcome of NTZ treatment, which may underpin an antiviral mechanism attributed to the thiazolide.

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代谢组学和抗氧化应激的调节参与了硝唑尼特抗甲型流感病毒的体外作用

高传染性甲型流感病毒(IAV)的流行仍然是对全球人类健康的主要威胁。Nitazoxanide (NTZ)对流感病毒具有有效的抗病毒特性。然而，小分子代谢物和抗氧化应激在NTZ抗流感病毒机制中的作用尚不完全清楚。本研究采用lc - ms代谢组学、流式细胞术、免疫印迹等方法，比较体外NTZ处理iav感染MDCK细胞后细胞代谢、ROS水平、抗氧化酶活性及Keap-1/Nrf2通路的变化。我们观察到，在iav感染的细胞中，NTZ处理显著改变了小分子的代谢，其中11种代谢物与NTZ高度相关。NTZ对病毒诱导的氧化应激也有显著的抑制作用。同时，NTZ处理后Nrf2通路和一些抗病毒活性调节蛋白被激活，保护细胞免受IAV损伤。因此，细胞内氧化状态的调节是NTZ治疗的主要结果，这可能是噻唑类药物抗病毒机制的基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta virologica 医学-病毒学

CiteScore

3.10

自引率

11.80%

发文量

审稿时长

>12 weeks

期刊介绍： Acta virologica is an international journal of predominantly molecular and cellular virology. Acta virologica aims to publish papers reporting original results of fundamental and applied research mainly on human, animal and plant viruses at cellular and molecular level. As a matter of tradition, also rickettsiae are included. Areas of interest are virus structure and morphology, molecular biology of virus-cell interactions, molecular genetics of viruses, pathogenesis of viral diseases, viral immunology, vaccines, antiviral drugs and viral diagnostics.