The Role and Therapeutic Potential of NF-kappa-B Pathway in Severe COVID-19 Patients

Abstract

Coronavirus disease 2019 (COVID-19) pandemic has affected health care systems worldwide. Severe presentations of COVID-19 such as severe pneumonia and acute respiratory distress syndrome (ARDS) have been associated with the post-viral activation and release of cytokine/chemokines which leads to a “cytokine storm” causing inflammatory response and destruction, mainly affecting the lungs. COVID-19 activation of transcription factor, NF-kappa B (NF-κB) in various cells such as macrophages of lung, liver, kidney, central nervous system, gastrointestinal system and cardiovascular system leads to production of IL-1, IL-2, IL-6, IL-12, TNF-α, LT-α, LT-β, GM-CSF, and various chemokines. The sensitised NF-κB in elderly and in patients with metabolic syndrome makes this set of population susceptible to COVID-19 and their worse complications, including higher mortality. Immunomodulation at the level of NF-κB activation and inhibitors of NF-κB (IκB) degradation along with TNF-α inhibition will potentially result in a reduction in the cytokine storm and alleviate the severity of COVID-19. Inhibition of NF-κB pathway has a potential therapeutic role in alleviating the severe form of COVID-19.

Zinc supplement augments the suppressive effects of repurposed drugs of NF-kappa B inhibitor on ACE2 expression in human lung cell lines in vitro

“…COVID-19 patients with severe COVID-19 displayed the uncontrolled NF-Brelated cytokine release syndrome (CRS), which is responsible for the poor prognosis and multiorgan defects (8). Thus, the pharmacological blockade of the NF-B signaling pathway can strongly represent a potential therapeutic consideration to attenuate COVID-19.…”

The Immunopathological and Histological Landscape of COVID-19-Mediated Lung Injury

“…Circulating sIL-6Rα can bind its ligand IL-6, causing the intracellular activation of the JAK/STAT3 pathway, which is a well-known trigger of NF-κB [ 73 ]. NF-κB is among the most important checkpoints involved in COVID-19-related proinflammatory events [ 62 , 74 ] and it is a pivotal protein complex involved in immune regulation [ 75 ].…”

The Pleiotropic Function of Human Sirtuins as Modulators of Metabolic Pathways and Viral Infections

“…Another example is the interaction of SIRTs with key transcription factors, such as NF-κB and FOXO1 [ 152 , 153 , 154 , 155 ]. The connection and crosstalk between NF-κB and SIRT1 in the regulation of inflammation (see Figure 8 ) and metabolic disorders have been investigated thoroughly by Kauppinen et al [ 152 ].…”

“…The inhibition of SIRT1 disrupts oxidative energy metabolism and stimulates the NF-κB-induced inflammatory responses. Hariharan et al, have reported that the SARS-CoV-2 components induce the activation of NF-κB in different cells, leading to the production of various chemokines (chemokines ‘storm’) [ 153 ] (see Figure 8 ).…”