Primidone blocks RIPK1-driven cell death and inflammation.
Cell Death Differ
; 28(5): 1610-1626, 2021 05.
Article
in English
| MEDLINE | ID: covidwho-957566
ABSTRACT
The receptor-interacting serine/threonine protein kinase 1 (RIPK1) is a key mediator of regulated cell death and inflammation. Recent studies suggest that RIPK1 inhibition would fundamentally improve the therapy of RIPK1-dependent organ damage in stroke, myocardial infarction, kidney failure, and systemic inflammatory response syndrome. Additionally, it could ameliorate or prevent multi-organ failure induced by cytokine release in the context of hyperinflammation, as seen in COVID-19 patients. Therefore, we searched for a RIPK1 inhibitor and present the aromatic antiepileptic and FDA-approved drug primidone (Liskantin®) as a potent inhibitor of RIPK1 activation in vitro and in a murine model of TNFα-induced shock, which mimics the hyperinflammatory state of cytokine release syndrome. Furthermore, we detected for the first time RIPK1 activation in the respiratory tract epithelium of hospitalized patients who tested positive for SARS-CoV-2 infection. Our data provide a strong rationale for evaluating the drug primidone in conditions of hyperinflammation in humans.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Primidone
/
Receptor-Interacting Protein Serine-Threonine Kinases
/
SARS-CoV-2
/
COVID-19
Type of study:
Experimental Studies
Limits:
Animals
/
Humans
Language:
English
Journal:
Cell Death Differ
Year:
2021
Document Type:
Article
Affiliation country:
S41418-020-00690-y
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