Modulation of IRAK enzymes as a therapeutic strategy against SARS-CoV-2 induced cytokine storm

Clin Exp Med. 2023 Oct;23(6):2909-2923. doi: 10.1007/s10238-023-01064-7. Epub 2023 Apr 15.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the current pandemic coronavirus disease 2019 (COVID-19). Dysregulated and excessive production of cytokines and chemokines, known as cytokine storm, is frequently seen in patients with severe COVID-19 disease and it can provoke a severe systematic inflammation in the patients. The IL-1R/TLRs/IRAKs signaling network is a key pathway in immune cells that plays a central role in regulating innate immunity and inflammatory responses via stimulating the expression and production of various proinflammatory molecules including cytokines. Modulation of IRAKs activity has been proposed to be a promising strategy in the treatment of inflammatory disorders. In this review, we highlight the biochemical properties of IRAKs and their role in regulating inflammatory molecular signaling pathways and discuss the potential targeting of IRAKs to suppress the SARS-CoV-2-induced cytokine storm in COVID-19 patients.

Keywords: Cytokine storm; IRAKs; Inflammation; SARS-CoV-2; Therapy.

Publication types

  • Review

MeSH terms

  • COVID-19*
  • Cytokine Release Syndrome / drug therapy
  • Cytokines
  • Humans
  • Immunity, Innate
  • SARS-CoV-2*

Substances

  • Cytokines