Inosine: A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation
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 lim...
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| Principais autores: | , , , , , , , , , , , |
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Elsevier,
2023-01-01T00:00:00Z.
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| 001 | doaj_431fac8d88d94b72b587dba4dfded26f | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Ningning Wang |e author |
| 700 | 1 | 0 | |a Entao Li |e author |
| 700 | 1 | 0 | |a Huifang Deng |e author |
| 700 | 1 | 0 | |a Lanxin Yue |e author |
| 700 | 1 | 0 | |a Lei Zhou |e author |
| 700 | 1 | 0 | |a Rina Su |e author |
| 700 | 1 | 0 | |a Baokun He |e author |
| 700 | 1 | 0 | |a Chengcai Lai |e author |
| 700 | 1 | 0 | |a Gaofu Li |e author |
| 700 | 1 | 0 | |a Yuwei Gao |e author |
| 700 | 1 | 0 | |a Wei Zhou |e author |
| 700 | 1 | 0 | |a Yue Gao |e author |
| 245 | 0 | 0 | |a Inosine: A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation |
| 260 | |b Elsevier, |c 2023-01-01T00:00:00Z. | ||
| 500 | |a 2095-1779 | ||
| 500 | |a 10.1016/j.jpha.2022.10.002 | ||
| 520 | |a 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-3β (GSK3β), inhibited the activation and nuclear translocation 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 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. | ||
| 546 | |a EN | ||
| 690 | |a Cytokine storm | ||
| 690 | |a Interleukin 6 (IL-6) | ||
| 690 | |a Inosine | ||
| 690 | |a SARS-CoV-2 | ||
| 690 | |a TANK-binding kinase 1 (TBK1) | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Journal of Pharmaceutical Analysis, Vol 13, Iss 1, Pp 11-23 (2023) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S2095177922000983 | |
| 787 | 0 | |n https://doaj.org/toc/2095-1779 | |
| 856 | 4 | 1 | |u https://doaj.org/article/431fac8d88d94b72b587dba4dfded26f |z Connect to this object online. |