Abstract
The term cytokine storm refers to an uncontrolled overproduction of soluble inflammatory markers known as cytokines and chemokines. Autoimmune destruction of the lungs triggered by the release of these inflammatory markers often induces acute respiratory distress syndrome (ARDS). ARDS is an emergency condition with a high mortality rate in COVID-19 patients. Dexamethasone is the first repurposed corticosteroid with life-saving efficacy in patients with severe SARS-CoV-2 infection. Dexamethasone has traditionally been known to suppress the production of inflammatory markers at the transcriptional level, but its role as a direct therapeutic to neutralize cytokines, chemokines, their receptors, and functionally critical SARS-CoV-2 proteins has not yet been explored. Herein, we demonstrated that dexamethasone binds with high affinity to interlukin-1 (IL-1), IL-6, IL-8, IL-12, IL-21, INF2, TGFβ-1, INF-γ, CXCL8, some of the receptors, IL-1R, IL-21R, IFNGR, INFAR, IL-6αR-gp130, ST2 and the SARS-CoV-2 protein NSP macro X, and 3CLpro, forming stable drug–protein complexes. Our work implied that dexamethasone has the potential to directly neutralize inflammatory markers, further supporting its life-saving potential in patients with severe manifestations of COVID-19.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected a quarter of a billion persons worldwide, resulting in over 5 million deaths as of 1 October 2021. several vaccines are available worldwide, the perpetual threat from the emergence of new variants has resulted in the COVID-19 pandemic still being one of the greatest public health crisis in modern history
The term “cytokine storm” originated from the observation that COVID-19 patients requiring intensive care unit (ICU) admission presented with much higher concentrations of TNF-α, CXCL10, and CCL2 in comparison to those with a less severe manifestation of the disease in which ICU admission was not necessary [1,3]
To evaluate the biding affinity of dexamethasone on the inflammatory proteins involved in COVID-19, including proinflammatory cytokines, chemokines, and their receptors, docking for the structurally binding of this drug on these proteins was employed (Figure 1 and Supplementary Table S1)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected a quarter of a billion persons worldwide, resulting in over 5 million deaths as of 1 October 2021. several vaccines are available worldwide, the perpetual threat from the emergence of new variants has resulted in the COVID-19 pandemic still being one of the greatest public health crisis in modern history. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected a quarter of a billion persons worldwide, resulting in over 5 million deaths as of 1 October 2021. Why are some patients asymptomatic, while others experience more severe forms of the disease, including acute respiratory distress syndrome (ARDS) [1]? Autoimmune destruction of the lungs triggered by the release of proinflammatory cytokines is emerging as a significant contributor to the morbidity and mortality in patients infected with SARSCoV-2 [2,3]. The term “cytokine storm” originated from the observation that COVID-19 patients requiring intensive care unit (ICU) admission presented with much higher concentrations of TNF-α, CXCL10, and CCL2 in comparison to those with a less severe manifestation of the disease in which ICU admission was not necessary [1,3]
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