New Proposal Involving Nanoformulated Melatonin Targeted to The Mitochondria as A Potential COVID-19 Treatment

Giménez, Virna Margarita Martín; Prado, Natalia Jorgelina; Diez, Emiliano; Manucha, Walter; Reíter, Russel J.

doi:10.2217/nnm-2020-0371

Cited by 23 publications

(17 citation statements)

References 23 publications

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“…Melatonin can be administered orally, sublingually, intranasally rectally as a suppository, intravenously, and as a skin patch containing absorbable melatonin. In addition to being available in conventional powdered form, it has been incorporated into nano-formulations, which may increase its bioavailability, especially at the mitochondrial level [235].…”

Section: References Indicating Melatonin Inhibits These Cell Typesmentioning

confidence: 99%

Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

Reíter

Sharma

Rosales-Corral

2021

IJMS

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Glucose is an essential nutrient for every cell but its metabolic fate depends on cellular phenotype. Normally, the product of cytosolic glycolysis, pyruvate, is transported into mitochondria and irreversibly converted to acetyl coenzyme A by pyruvate dehydrogenase complex (PDC). In some pathological cells, however, pyruvate transport into the mitochondria is blocked due to the inhibition of PDC by pyruvate dehydrogenase kinase. This altered metabolism is referred to as aerobic glycolysis (Warburg effect) and is common in solid tumors and in other pathological cells. Switching from mitochondrial oxidative phosphorylation to aerobic glycolysis provides diseased cells with advantages because of the rapid production of ATP and the activation of pentose phosphate pathway (PPP) which provides nucleotides required for elevated cellular metabolism. Molecules, called glycolytics, inhibit aerobic glycolysis and convert cells to a healthier phenotype. Glycolytics often function by inhibiting hypoxia-inducible factor-1α leading to PDC disinhibition allowing for intramitochondrial conversion of pyruvate into acetyl coenzyme A. Melatonin is a glycolytic which converts diseased cells to the healthier phenotype. Herein we propose that melatonin’s function as a glycolytic explains its actions in inhibiting a variety of diseases. Thus, the common denominator is melatonin’s action in switching the metabolic phenotype of cells.

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Section: References Indicating Melatonin Inhibits These Cell Typesmentioning

confidence: 99%

Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

Reíter

Sharma

Rosales-Corral

2021

IJMS

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“…Viral infection with SARS-CoV-2 can cause severe inflammatory responses and oxidative stress; the use of melatonin may be able to attenuate some of these reactions. SARS-CoV-2 enters alveolar epithelial cells via ACE2, facilitated by the S1 and S2 subunits of the S spike protein on the virus ( 36 ). S1 allows attachment to ACE 2, while S2 mediates fusion of the virus with the cell membrane ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Melatonin for the Early Treatment of COVID-19: A Narrative Review of Current Evidence and Possible Efficacy

et al. 2021

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Objective To date, there are no FDA approved medications for treatment of early COVID-19 infection. Recently, use of melatonin, a naturally occurring tryptophan-derivative synthesized in the pineal gland and immune cells, has been suggested as an early treatment option for COVID-19. Melatonin has known anti-inflammatory, immunomodulatory, and protective antioxidant mechanisms that may attenuate the severity of COVID-19 symptoms. The objective of the present narrative review is to discuss the use of melatonin as an early treatment option on the first day of diagnosis for COVID-19. Methods The MeSH terms “COVID-19” and “viral diseases” were manually searched on PubMed and relevant articles were included. Results Results showed that melatonin acts to reduce reactive-oxygen-species mediated damage, cytokine-induced inflammation, and lymphopenia in viral diseases similar to COVID-19. Conclusions These conclusions provide evidence for potential benefits in melatonin use for COVID-19 treatment as early as the day of diagnosis.

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“…Melatonin, such as many other antiparasitic drugs-ivermectin [205][206][207][208][209], doxycycline [210][211][212], metronidazole [213], mefloquine [214], and hydroxychloroquine [215,216]has been suggested as a possible adjuvant agent in the treatment of coronavirus disease 2019 (COVID-19) infection [217][218][219][220][221]. Due to its anti-inflammatory, antioxidant and potent mitoprotective properties, melatonin might be beneficial in the preservation of mitochondrial functions and neuro-and cardioprotection during infections, whereas clarification of its mechanism of action as antiparasitic agent would be an interesting topic for further research.…”

Section: The Role Of Melatonin In the Treatment Of The Protozoan Parasitic Infectionsmentioning

confidence: 99%

Molecular Mechanisms of Melatonin-Mediated Cell Protection and Signaling in Health and Disease

Kopustinskienė

Bernatonienė

2021

Pharmaceutics

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Melatonin, an endogenously synthesized indolamine, is a powerful antioxidant exerting beneficial action in many pathological conditions. Melatonin protects from oxidative stress in ischemic/reperfusion injury, neurodegenerative diseases, and aging, decreases inflammation, modulates the immune system, inhibits proliferation, counteracts the Warburg effect, and promotes apoptosis in various cancer models. Melatonin stimulates antioxidant enzymes in the cells, protects mitochondrial membrane phospholipids, especially cardiolipin, from oxidation thus preserving integrity of the membranes, affects mitochondrial membrane potential, stimulates activity of respiratory chain enzymes, and decreases the opening of mitochondrial permeability transition pore and cytochrome c release. This review will focus on the molecular mechanisms of melatonin effects in the cells during normal and pathological conditions and possible melatonin clinical applications.

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New Proposal Involving Nanoformulated Melatonin Targeted to The Mitochondria as A Potential COVID-19 Treatment

Cited by 23 publications

References 23 publications

Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

Melatonin for the Early Treatment of COVID-19: A Narrative Review of Current Evidence and Possible Efficacy

Molecular Mechanisms of Melatonin-Mediated Cell Protection and Signaling in Health and Disease

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