Dapsone as treatment adjunct in ARDS

Kast, Richard E.

doi:10.1080/01902148.2020.1753266

Cited by 17 publications

(19 citation statements)

References 50 publications

(60 reference statements)

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“…Two out of 13 patients who underwent a brain MRI (Magnetic Resonance Imaging) had single acute ischemic strokes. Data are lacking to determine which of these features were due to critical illness-related encephalopathy, cytokines, the effect or withdrawal of medication, and which features were specific to SARS-CoV-2 infection [ 35 , 36 ]. To date, clinical studies have shown that DDS can block disease progression due to critical illness (inflammation)-related encephalopathy or immune-related diseases [ 36 , 37 , 62 , 63 ].…”

Section: Resultsmentioning

confidence: 99%

4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor

Lee

Sohn

et al. 2020

IJMS

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The aim of this study is to examine the use of an inflammasome competitor as a preventative agent. Coronaviruses have zoonotic potential due to the adaptability of their S protein to bind receptors of other species, most notably demonstrated by SARS-CoV. The binding of SARS-CoV-2 to TLR (Toll-like receptor) causes the release of pro-IL-1β, which is cleaved by caspase-1, followed by the formation and activation of the inflammasome, which is a mediator of lung inflammation, fever, and fibrosis. The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome is implicated in a variety of human diseases including Alzheimer’s disease (AD), prion diseases, type 2 diabetes, and numerous infectious diseases. By examining the use of 4,4′-diaminodiphenyl sulfone (DDS) in the treatment of patients with Hansen’s disease, also diagnosed as Alzheimer’s disease, this study demonstrates the diverse mechanisms involved in the activation of inflammasomes. TLRs, due to genetic polymorphisms, can alter the immune response to a wide variety of microbial ligands, including viruses. In particular, TLR2Arg677Trp was reported to be exclusively present in Korean patients with lepromatous leprosy (LL). Previously, mutation of the intracellular domain of TLR2 has demonstrated its role in determining the susceptibility to LL, though LL was successfully treated using a combination of DDS with rifampicin and clofazimine. Of the three tested antibiotics, DDS was effective in the molecular regulation of NLRP3 inflammasome activators that are important in mild cognitive impairment (MCI), Parkinson’s disease (PD), and AD. The specific targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by DDS may be responsible for its observed preventive effects, functioning as a competitor.

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Section: Resultsmentioning

confidence: 99%

4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor

Lee

Sohn

et al. 2020

IJMS

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“…Degranulating neutrophils have a key role in the development of capillary injury and leakage and hyaline deposition. These events may progress to ARDS or a more fatally diffuse alveolar damage 11 . The key role of neutrophils in the pathogenesis of ALI/ARDS has also been shown in animal and clinical studies.…”

Section: What Is Known and Objectivementioning

confidence: 89%

Neutrophil elastase inhibitor (sivelestat) may be a promising therapeutic option for management of acute lung injury/acute respiratory distress syndrome or disseminated intravascular coagulation in COVID‐19

et al. 2020

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What is known and objective This article summarizes the effects of sivelestat on acute lung injury/acute respiratory distress syndrome (ALI/ARDS) or ARDS with coagulopathy, both of which are frequently seen in patients with COVID‐19. Comment COVID‐19 patients are more susceptible to thromboembolic events, including disseminated intravascular coagulation (DIC). Various studies have emphasized the role of neutrophil elastase (NE) in the development of DIC in patients with ARDS and sepsis. It has been shown that NE inhibition by sivelestat mitigates ALI through amelioration of injuries in alveolar epithelium and vascular endothelium, as well as reversing the neutrophil‐mediated increased vascular permeability. What is new and conclusions Sivelestat, a selective NE inhibitor, has not been evaluated for its possible therapeutic effects against SARS‐CoV‐2 infection. Based on its promising beneficial effects in underlying complications of COVID‐19, sivelestat could be considered as a promising modality for better management of COVID‐19–induced ALI/ARDS or coagulopathy.

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“…Indeed, the significant role of neutrophils in the promotion of ARdS-related alveolal damage was supported by a report in sepsis ARdS patients, where high neutrophil counts in bronchiolar lavage material harvested late in ARdS progression was associated with reduced patient survival (26). Hence, it has been proposed that the sulphone dapsone may show efficacy in COVID-19 related ARDS, as the drug is highly and rapidly effective at inhibiting cytokine-mediated neutrophil chemotaxis and respiratory burst in a variety of therapeutic contexts (27). Efficacy of Dapsone in the treatment of Pneumocystis pneumonia suggests it will penetrate the lung tissue sufficiently to attenuate neutrophil activity.…”

Section: Clinical Aspects Of Covid-19 Infections; Acute Respiratory Dmentioning

confidence: 92%

“…Efficacy of Dapsone in the treatment of Pneumocystis pneumonia suggests it will penetrate the lung tissue sufficiently to attenuate neutrophil activity. The haemotoxicity of the drug can be ameliorated with concomitant cimetidine administration (27,28).…”

Section: Clinical Aspects Of Covid-19 Infections; Acute Respiratory Dmentioning

confidence: 99%

A dissection of SARS‑CoV2 with clinical implications (Review)

Stancioiu¹,

Papadakis

Kteniadakis

et al. 2020

Int J Mol Med

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We are being confronted with the most consequential pandemic since the Spanish flu of 1918-1920 to the extent that never before have 4 billion people quarantined simultaneously; to address this global challenge we bring to the forefront the options for medical treatment and summarize SARS-coV2 structure and functions, immune responses and known treatments. Based on literature and our own experience we propose new interventions, including the use of amiodarone, simvastatin, pioglitazone and curcumin. In mild infections (sore throat, cough) we advocate prompt local treatment for the naso-pharynx (inhalations; aerosols; nebulizers); for moderate to severe infections we propose a tried-and-true treatment: the combination of arginine and ascorbate, administered orally or intravenously. The material is organized in three sections: i) Clinical aspects of COVID-19; acute respiratory distress syndrome (ARdS); known treatments; ii) Structure and functions of SARS-coV2 and proposed antiviral drugs; iii) The combination of arginine-ascorbate. Contents 1. Clinical aspects of COVID-19 infections; acute respiratory distress syndrome (ARdS); known and potential treatments 2. SARS-coV2 molecules and proposed antiviral drugs 3. The combination of arginine-ascorbate

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Dapsone as treatment adjunct in ARDS

Cited by 17 publications

References 50 publications

4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor

4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor

Neutrophil elastase inhibitor (sivelestat) may be a promising therapeutic option for management of acute lung injury/acute respiratory distress syndrome or disseminated intravascular coagulation in COVID‐19

A dissection of SARS‑CoV2 with clinical implications (Review)

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