Inosine: A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation

文献类型： 外文期刊

第一作者： Wang, Ningning

作者： Wang, Ningning;Deng, Huifang;Yue, Lanxin;Zhou, Lei;Lai, Chengcai;Li, Gaofu;Zhou, Wei;Gao, Yue;Wang, Ningning;Gao, Yue;Li, Entao;Su, Rina;Gao, Yuwei;Su, Rina;He, Baokun

作者机构：

关键词： Cytokine storm; Interleukin 6 (IL-6); Inosine; SARS-CoV-2; TANK-binding kinase 1 (TBK1)

期刊名称：JOURNAL OF PHARMACEUTICAL ANALYSIS （ 影响因子：8.8； 五年影响因子：7.2 ）

ISSN： 2095-1779

年卷期： 2023 年 13 卷 1 期

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收录情况： SCI

摘要： Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storms constitute the primary cause of coronavirus disease 19 (COVID-19) progression, severity, criticality, and death. Glucocorticoid and anti-cytokine therapies are frequently administered to treat COVID-19, but have limited clinical efficacy in severe and critical cases. Nevertheless, the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this infection. We found that the broad-spectrum anti-inflammatory agent inosine downregulated proinflammatory interleukin (IL)-6, upregulated anti-inflammatory IL-10, and ameliorated acute inflammatory lung injury caused by multiple infectious agents. Inosine significantly improved survival in mice infected with SARS-CoV-2. It indirectly impeded TANK-binding kinase 1 (TBK1) phosphorylation by binding stimulator of interferon genes (STING) and glycogen synthase kinase-3 beta (GSK3 beta), inhibited the activation and nuclear translocation of the downstream transcription factors interferon regulatory factor (IRF3) and nuclear factor kappa B (NF-kappa B), and downregulated IL-6 in the sera and lung tissues of mice infected with lipopolysaccharide (LPS), H1N1, or SARS-CoV-2. Thus, inosine administration is feasible for clinical anti-inflammatory therapy against severe and critical COVID-19. Moreover, targeting TBK1 is a promising strategy for inhibiting cytokine storms and mitigating acute inflammatory lung injury induced by SARS-CoV-2 and other infectious agents. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Xi'an Jiaotong University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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