Melatonin for the treatment of sepsis: the scientific rationale

Biancatelli, Ruben Manuel Luciano Colunga; Berrill, Max; Mohammed, Yassen H.; Marik, Paul E.

doi:10.21037/jtd.2019.12.85

Cited by 79 publications

(76 citation statements)

References 143 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Oral melatonin use by humans is generally considered safe, with minor side effects including headache, drowsiness, etc. (43). To date, the best dose of melatonin in older adults has not been determined, as its endogenous levels are subject to altered pharmacokinetics.…”

Section: Melatonin In Covid-19 Outbreak: Prevention In the Populationmentioning

confidence: 99%

“…Melatonin has been shown to be clinically useful in sepsis (43), where the clinical features parallel those of COVID-19 viral infection; moreover, melatonin has been demonstrated to relieve many of the symptoms of other viral infections (17)(18)(19)(20)(21)48). Given the current worldwide situation and in consideration of evidence-based medicine, the efficacy of melatonin and its high pharmacological safety profile supports its use in the treatment of infectious diseases, such as COVID-19.…”

Section: Melatonin In Covid-19 Outbreak: Treatment In the Hospitalmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19

et al. 2020

Self Cite

View full text Add to dashboard Cite

The coronavirus, COVID-19, has infected hundreds of thousands and killed tens of thousands of individuals worldwide. This highly infectious condition continues to ravage the world population and has yet to reach it peak infective rate in some countries. Many conventional drugs including hydroxychloroquine/chloroquine, lopinavir, remdesivir, etc., have been repurposed as treatments for this often deadly disease, but there is no specifically-designed effective drug available; also, the drugs mentioned have significant side effects and their efficacy is unknown. New drugs and vaccines are being designed as COVID-19 treatment, but their development and testing will require months to years. Time is not a luxury that this crisis has. Thus, there is a serious unmet need for the identification of currently-available and safe molecules which can be used to slow or treat COVID-19 disease. Here, we suggest melatonin be given consideration for prophylactic use or treatment alone or in combination with other drugs. Melatonin's multiple actions as an anti-inflammatory, anti-oxidant, and anti-viral (against other viruses) make it a reasonable choice for use. Melatonin is readily available, can be easily synthesized in large quantities, is inexpensive, has a very high safety profile and can be easily self-administered. Melatonin is endogenously-produced molecule in small amounts with its production diminishing with increased age. Under the current critical conditions, large doses of melatonin alone or in combination with currently-recommended drugs, e.g., hydroxychloroquine/chloroquine, to resist COVID-19 infection would seem judicious.

show abstract

Section: Melatonin In Covid-19 Outbreak: Prevention In the Populationmentioning

confidence: 99%

Section: Melatonin In Covid-19 Outbreak: Treatment In the Hospitalmentioning

confidence: 99%

Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…iNOS) with a consequent reduction of peroxynitrite formation [79]. Several studies have demonstrated the therapeutic efficacy of melatonin in controlling septic conditions induced by toxic drugs or infection [80][81][82].…”

Section: Melatoninmentioning

confidence: 99%

COVID-19: Rational discovery of the therapeutic potential of Melatonin as a SARS-CoV-2 main Protease Inhibitor

Feitosa¹,

Júnior²,

Neto³

et al. 2020

Int. J. Med. Sci.

View full text Add to dashboard Cite

The SARS-CoV-2 spread quickly across the globe. The World Health Organization (WHO) on March 11 declared COVID-19 a pandemic. The mortality rate, hospital disorders and incalculable economic and social damages, besides the unproven efficacy of the treatments evaluated against COVID-19, raised the need for immediate control of this disease. Therefore, the current study employed in silico tools to rationally identify new possible SARS-CoV-2 main protease (Mpro) inhibitors. That is an enzyme conserved among the coronavirus species; hence, the identification of an Mpro inhibitor is to make it a broad-spectrum drug. Molecular docking studies described the binding sites and the interaction energies of 74 Mpro-ligand complexes deposited in the Protein Data Bank (PDB). A structural similarity screening was carried out in order to identify possible Mpro ligands that show additional pharmacological properties against COVID-19. We identified 59 hit compounds and among them, melatonin stood out due to its prominent immunomodulatory and anti-inflammatory activities; it can reduce oxidative stress, defence cell mobility and efficiently combat the cytokine storm and sepsis. In addition, melatonin is an inhibitor of calmodulin, an essential intracellular component to maintain angiotensin-converting enzyme 2 (ACE-2) on the cell surface. Interestingly, one of the most promising hits in our docking study was melatonin. It revealed better interaction energy with Mpro compared to ligands in complexes from PDB. Consequently, melatonin can have response potential in early stages for its possible effects on ACE-2 and Mpro, although it is also promising in more severe stages of the disease for its action against hyper-inflammation. These results definitely do not confirm antiviral activity, but can rather be used as a basis for further preclinical and clinical trials.

show abstract

“…[8][9][10][11][12][13][14][15][16][17] The accumulated data on physiological and pharmacological functions of melatonin underscore its potential clinical significance. 18,19 The free radical scavenging ability is noteworthy, which suppresses oxidative stress and cellular damage through endogenous redox modulations and key downstream signaling events. [20][21][22] Further, melatonin is implicated in mediating neuroendocrine-immune system, which may facilitate the cross talk between the pineal gland and the immune system.…”

Section: Introductionmentioning

confidence: 99%

Melatonin restores neutrophil functions and prevents apoptosis amid dysfunctional glutathione redox system

NaveenKumar

Hemshekhar

Jagadish

et al. 2020

Journal of Pineal Research

View full text Add to dashboard Cite

Melatonin is a chronobiotic hormone, which can regulate human diseases like cancer, atherosclerosis, respiratory disorders, and microbial infections by regulating redox system. Melatonin exhibits innate immunomodulation by communicating with immune system and influencing neutrophils to fight infections and inflammation. However, sustaining redox homeostasis and reactive oxygen species (ROS) generation in neutrophils are critical during chemotaxis, oxidative burst, phagocytosis, and neutrophil extracellular trap (NET) formation. Therefore, endogenous antioxidant glutathione (GSH) redox cycle is highly vital in regulating neutrophil functions. Reduced intracellular GSH levels and glutathione reductase (GR) activity in the neutrophils during clinical conditions like autoimmune disorders, neurological disorders, diabetes, and microbial infections lead to dysfunctional neutrophils. Therefore, we hypothesized that redox modulators like melatonin can protect neutrophil health and functions under GSH and GR activity–deficient conditions. We demonstrate the dual role of melatonin, wherein it protects neutrophils from oxidative stress‐induced apoptosis by reducing ROS generation; in contrast, it restores neutrophil functions like phagocytosis, degranulation, and NETosis in GSH and GR activity–deficient neutrophils by regulating ROS levels both in vitro and in vivo. Melatonin mitigates LPS‐induced neutrophil dysfunctions by rejuvenating GSH redox system, specifically GR activity by acting as a parallel redox system. Our results indicate that melatonin could be a potential auxiliary therapy to treat immune dysfunction and microbial infections, including virus, under chronic disease conditions by restoring neutrophil functions. Further, melatonin could be a promising immune system booster to fight unprecedented pandemics like the current COVID‐19. However, further studies are indispensable to address the clinical usage of melatonin.

show abstract

Melatonin for the treatment of sepsis: the scientific rationale

Cited by 79 publications

References 143 publications

Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19

Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19

COVID-19: Rational discovery of the therapeutic potential of Melatonin as a SARS-CoV-2 main Protease Inhibitor

Melatonin restores neutrophil functions and prevents apoptosis amid dysfunctional glutathione redox system

Contact Info

Product

Resources

About