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

Journal of Pharmaceutical Analysis

Available online 22 October 2022

Journal of Pharmaceutical AnalysisHighlights•

Inosine significantly improved the survival rate of SARS-CoV-2-infected mice.

Inosine obviously abrogated evoked excessive IL-6 expression but elevated IL-10 content, and eventually ameliorated acute inflammatory lung injury caused by multiple infectious agents.

Inosine indirectly interfered with the phosphorylation of TBK1 via binding to STING and GSK3β, leading to remarkable decreases in IL-6 release in serum and lung tissue of mice infected with LPS, H1N1 or SARS-CoV-2.

Abstract

SARS-CoV-2-induced cytokine storms constitute the primary cause of COVID-19 progression, severity, criticality, and death. Glucocorticoid and anti-cytokine therapies have been frequently administered to treat COVID-19 but have had 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 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-3β (GSK3β), inhibited the activation and nuclear translocation of the downstream transcription factors IRF3 and NF-κB, 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.

Keywords

Cytokine storm

Interleukin 6

Inosine

SARS-CoV-2

TANK-binding kinase 1 (TBK1)

© 2022 The Author(s). Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.

留言 (0)

沒有登入
gif