التفاصيل البيبلوغرافية
| العنوان: |
Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection. |
| المؤلفون: |
Ullah, TR, Johansen, MD, Balka, KR, Ambrose, RL, Gearing, LJ, Roest, J, Vivian, JP, Sapkota, S, Jayasekara, WSN, Wenholz, DS, Aldilla, VR, Zeng, J, Miemczyk, S, Nguyen, DH, Hansbro, NG, Venkatraman, R, Kang, JH, Pang, ES, Thomas, BJ, Alharbi, AS, Rezwan, R, O'Keeffe, M, Donald, WA, Ellyard, JI, Wong, W, Kumar, N, Kile, BT, Vinuesa, CG, Kelly, GE, Laczka, OF, Hansbro, PM, De Nardo, D, Gantier, MP |
| بيانات النشر: |
NATURE PORTFOLIO |
| سنة النشر: |
2024 |
| المجموعة: |
University of Technology Sydney: OPUS - Open Publications of UTS Scholars |
| مصطلحات موضوعية: |
Animals, Mice, I-kappa B Kinase, Disease Models, Animal, COVID-19, SARS-CoV-2, Inflammation, Interferon Type I |
| الوصف: |
TANK-binding kinase 1 (TBK1) is a key signalling component in the production of type-I interferons, which have essential antiviral activities, including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement of type-I interferons is associated with damaging hyper-inflammation found in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to these responses is unknown. Here we find that the small molecule idronoxil inhibits TBK1/IKKε signalling through destabilisation of TBK1/IKKε protein complexes. Treatment with idronoxil, or the small molecule inhibitor MRT67307, suppresses TBK1/IKKε signalling and attenuates cellular and molecular lung inflammation in SARS-CoV-2-challenged mice. Our findings additionally demonstrate that engagement of STING is not the major driver of these inflammatory responses and establish a critical role for TBK1/IKKε signalling in SARS-CoV-2 hyper-inflammation. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
Electronic; application/pdf |
| اللغة: |
English |
| تدمد: |
2041-1723 |
| Relation: |
http://purl.org/au-research/grants/nhmrc/1175134; Nat Commun; Nat Commun, 2023, 14, (1), pp. 5666; http://hdl.handle.net/10453/174954 |
| الاتاحة: |
http://hdl.handle.net/10453/174954 |
| Rights: |
info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.C850533E |
| قاعدة البيانات: |
BASE |
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