Inosine:A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation
- Author:
Ningning WANG
1
,
2
;
Entao LI
;
Huifang DENG
;
Lanxin YUE
;
Lei ZHOU
;
Rina SU
;
Baokun HE
;
Chengcai LAI
;
Gaofu LI
;
Yuwei GAO
;
Wei ZHOU
;
Yue GAO
Author Information
1. Department of Pharmaceutical Sciences,Beijing Institute of Radiation Medicine,Beijing,100850,China
2. Tianjin University of Traditional Chinese Medicine,Tianjin,301617,China
- Keywords:
Cytokine storm;
Interleukin 6(IL-6);
Inosine;
SARS-CoV-2;
TANK-binding kinase 1(TBK1)
- From:
Journal of Pharmaceutical Analysis
2023;13(1):11-23
- CountryChina
- Language:Chinese
-
Abstract:
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.Gluco-corticoid 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 mul-tiple 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 trans-location of the downstream transcription factors interferon regulatory factor(IRF3)and nuclear factor kappa B(NF-κB),and downregulated IL-6 in the sera and lung tissues of mice infected with lipopoly-saccharide(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.
