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The triumvirate of NF-κB, inflammation and cytokine storm in COVID-19.
Attiq, Ali; Yao, Lui Jin; Afzal, Sheryar; Khan, Mansoor Ali.
  • Attiq A; Department of Pharmacology and Toxicology, Faculty of Pharmacy, MAHSA University, Bandar Saujana Putra, 42610 Jenjarom, Selangor, Malaysia. Electronic address: aliattiq@mahsa.edu.my.
  • Yao LJ; Kuala Balah Health Clinic (Klinik Kesihatan Kuala Balah), Kuala Balah, 17600 Jeli, Kelantan, Malaysia.
  • Afzal S; Department of Pharmacology and Toxicology, Faculty of Pharmacy, MAHSA University, Bandar Saujana Putra, 42610 Jenjarom, Selangor, Malaysia.
  • Khan MA; COVID-19 Vaccination Centres, University College London Hospitals, National Health Service, N10QH London, England.
Int Immunopharmacol ; 101(Pt B): 108255, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1549847
ABSTRACT
The coronavirus disease (COVID-19) has once again reminded us of the significance of host immune response and consequential havocs of the immune dysregulation. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) inflicts severe complications to the infected host, including cough, dyspnoea, fever, septic shock, acute respiratory distress syndrome (ARDs), and multiple organ failure. These manifestations are the consequence of the dysregulated immune system, which gives rise to excessive and unattended production of pro-inflammatory mediators. Elevated circulatory cytokine and chemokine levels are accompanied by spontaneous haemorrhage, thrombocytopenia and systemic inflammation, which are the cardinal features of life-threatening cytokine storm syndrome in advanced COVID-19 diseases. Coronavirus hijacked NF-kappa B (NF-κB) is responsible for upregulating the expressions of inflammatory cytokine, chemokine, alarmins and inducible enzymes, which paves the pathway for cytokine storm. Given the scenario, the systemic approach of simultaneous inhibition of NF-κB offers an attractive therapeutic intervention. Targeted therapies with proteasome inhibitor (VL-01, bortezomib, carfilzomib and ixazomib), bruton tyrosine kinase inhibitor (acalabrutinib), nucleotide analogue (remdesivir), TNF-α monoclonal antibodies (infliximab and adalimumab), N-acetylcysteine and corticosteroids (dexamethasone), focusing the NF-κB inhibition have demonstrated effectiveness in terms of the significant decrease in morbidity and mortality in severe COVID-19 patients. Hence, this review highlights the activation, signal transduction and cross-talk of NF-κB with regard to cytokine storm in COVID-19. Moreover, the development of therapeutic strategies based on NF-κB inhibition are also discussed herein.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: NF-kappa B / Cytokine Release Syndrome / SARS-CoV-2 / COVID-19 Type of study: Randomized controlled trials Limits: Animals / Humans Language: English Journal: Int Immunopharmacol Journal subject: Allergy and Immunology / Pharmacology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: NF-kappa B / Cytokine Release Syndrome / SARS-CoV-2 / COVID-19 Type of study: Randomized controlled trials Limits: Animals / Humans Language: English Journal: Int Immunopharmacol Journal subject: Allergy and Immunology / Pharmacology Year: 2021 Document Type: Article