Viral Diseases
Medical Studies on Melatonin – Viral Diseases
Melatonin is, in a sense, a star among the body’s natural antioxidants, because it fights and neutralises free radicals down to the cellular level, protecting DNA from damage. But its potential as a free radical catcher doesn’t stop there – melatonin is also able to stimulate the cells’ production of further free-radical interceptors, which further boosts its anti-oxidative effect.
Strengthening the immune system
These properties are of particular interest for fighting and treating viral diseases such as Ebola and herpes as well as those caused by coronavirus, such as 2019-nCoV. In addition, melatonin boosts the immune system, which is a key factor of any successful therapy, especially during viral pandemics.
Melatonin protects cells
Viruses always need host cells to replicate in the human organism. One way to treat viral diseases is therefore based on preventing this process. Studies are increasingly suggesting that coronaviruses in particular attack human cells via ACE2 (angiotensin-converting enzyme 2).
Melatonin and coronaviruses
Melatonin indirectly regulates ACE2 expression and has been deemed to be a promising agent in the fight against coronavirus in several studies, as it could prevent infection of these cells. At the same time, it also prevents the premature cell death of these infected cells (apoptosis), which not only slows the spread of infection but also buys the immune system more time to adapt to the infection.
Medical Studies on Melatonin – Viral Diseases
Plasticity of glucose metabolism in activated immune cells: advantages for melatonin inhibition of COVID-19 disease
2020-06 Reiter RJ, Sharma R, Ma Q, Liu C, Manucha W, Abreu-Gonzalez P, Dominguez-Rodriguez A
COVID-19 has infected hundreds of thousands and killed tens of thousands of people worldwide and it continues to ravage societies as well as fiscal and economic stability of several countries. Currently, several drugs that were designed for other conditions have been repurposed to counter the COVID-19 pandemic. Some have modest efficacy in resisting this disease, but all of them have significant toxicity. Several pharmaceutical companies are rushing to develop vaccines, but their availability is 8 to 12 months in the future. In the meantime, readily available and affordable molecules that will have utility as COVID-19 antidotes are being sought.
Melatonin, cardiovascular disease and COVID-19: A potential therapeutic strategy?
2020-06 Dominguez-Rodriguez A, Abreu-Gonzalez P, Marik PE, Reiter RJ
The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. SARS-CoV-2 induced endothelial dysfunction and cardiovascular injury are probably initiated by increases in the phosphorylation levels of JAK2 and STAT3 and resultant reactive oxygen species (ROS) formation. These pathological alterations are speculated to be strikingly reversed by melatonin.
Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series
2020-06 Castillo RR, Quizon GRA, Juco MJM, Roman ADE, de Leon DG, Punzalan FER, Guingon RBL, Morales DD, Tan DX, Reiter RJ
Treatment for coronavirus disease 2019 (COVID19) pneumonia remains empirical and the search for therapies that can improve outcomes continues. Melatonin has been shown to have anti-inflammatory, antioxidant, and immune-modulating effects that may address key pathophysiologic mechanisms in the development and progression of acute respiratory distress syndrome (ARDS), which has been implicated as the likely cause of death in COVID19.
COVID-19 pathophysiology: interactions of gut microbiome, melatonin, vitamin D, stress, kynurenine and the alpha 7 nicotinic receptor: Treatment implications
2020-06 Anderson G, Reiter RJ
As data emerges on the pathophysiological underpinnings of severe acute respiratory syndrome coronavirus (SARS-CoV)-2, it is clear that there are considerable variations in its susceptibility and severity/fatality, which give indications as to its pathophysiology and treatment.
Melatonin Inhibits COVID-19-induced Cytokine Storm by Reversing Aerobic Glycolysis in Immune Cells: A Mechanistic Analysis
2020-06 Reiter RJ, Sharma R, Ma Q, Dominquez-Rodriguez A, Marik PE, Abreu-Gonzalez P
The pathogenesis of a COVID-19 respiratory infection, in a major way, is related to what is referred to as the cytokine storm [cytokine storm syndrome (CSS, hypercytokinemia, etc.], i.e., it is a hyper-inflammatory response.
Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19
2020-05 Reiter RJ, Abreu-Gonzalez P, Marik PE, Dominguez-Rodriguez A
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.
Network-based Drug Repurposing for Human Coronavirus.
2020-04 Zhou Y, Hou Y, Shen J, Huang Y, Martin W, Cheng F
Human Coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle east respiratory syndrome coronavirus (MERS-CoV), and 2019 novel coronavirus (2019-nCoV), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV.
COVID-19: Melatonin as a potential adjuvant treatment.
2020-04 Zhang R, Wang X, Ni L, Di X, Ma B, Niu S, Liu C, Reiter RJ
This article summarizes the likely benefits of melatonin in the attenuation of COVID-19 based on its putative pathogenesis.
Can melatonin reduce the severity of COVID-19 pandemic?
2020-04 Shneider A, Kudriavtsev A, Vakhrusheva A
The current COVID-19 pandemic is one of the most devastating events in recent history. The virus causes relatively minor damage to young, healthy populations, imposing life-threatening danger to the elderly and people with diseases of chronic inflammation. Therefore, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks.
Melatonin in Mitochondria: Mitigating Clear and Present Dangers.
2020-04 Reiter RJ, Ma Q, Sharma R
In cancer cells, glucose is primarily metabolized to pyruvate and then to lactate in the cytosol.
Treatment of Ebola and other infectious diseases: melatonin “goes viral”.
2020-04 Reiter RJ, Sharma R
This review summarizes published reports on the utility of melatonin as a treatment for virus-mediated diseases. Of special note are the data related to the role of melatonin in influencing Ebola virus disease.
PAK1-blockers: Potential Therapeutics against COVID-19.
2020-04 Maruta H, He H
PAK1 (RAC/CDC42-activated kinase 1) is the major “pathogenic” kinase whose abnormal activation causes a wide variety of diseases/disorders including cancers, inflammation, malaria and pandemic viral infection including influenza, HIV and COVID-19.
Melatonin: Roles in influenza, Covid-19, and other viral infections.
2020-04 Anderson G, Reiter RJ
There is a growing appreciation that the regulation of the melatonergic pathways, both pineal and systemic, may be an important aspect in how viruses drive the cellular changes that underpin their control of cellular function.
Mitochondria: the birth place, battle ground and the site of melatonin metabolism cells.
2019-12 Tan DX, Reiter RJ
It was a surprising discovery when mitochondria, as the power houses of cells, were also found to synthesize the potent mitochondrial targeted antioxidant, melatonin. The melatonin synthetic enzyme serotonin N-acetyltransferase (SNAT) was found in matrix and also in the intermembrane space of mitochondria.
Melatonin: A new inhibitor agent for cervical cancer treatment.
2019-12 Shafabakhsh R, Reiter RJ, Mirzaei H, Teymoordash SN, Asemi Z
Cervical cancer is one of the most common cancers between women and is known as the third leading cause of female cancer related deaths annually. Its detection in early stages allows it to be a preventable and generally treatable disease.
Measurement of melatonin, indole-dioxygenase, IL-6, IL-18, ferritin, CRP, and total homocysteine levels during herpes zoster.
2019-04 Khazan M, Nasiri S, Riahi SM, Robati RM, Hedayati M
The risk of herpes zoster (HZ) increases with age and declining immune function. Increased oxidative stress and inflammatory conditions may cause a negative impact on the immune responses.
Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks.
2019-03 Hardeland R
Aging and various age-related diseases are associated with reductions in melatonin secretion, proinflammatory changes in the immune system, a deteriorating circadian system, and reductions in sirtuin-1 (SIRT1) activity.
Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas.
2017-11 Reiter RJ, Rosales-Corral S, Tan DX, Jou MJ, Galano A, Xu B
Melatonin is an ancient antioxidant. After its initial development in bacteria, it has been retained throughout evolution such that it may be or may have been present in every species that have existed. Even though it has been maintained throughout evolution during the diversification of species, melatonin’s chemical structure has never changed; thus, the melatonin …
Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas. Read More »
Melatonin as an antioxidant: under promises but over delivers.
2016-10 Reiter RJ, Mayo JC, Tan DX, Sainz RM, Alatorre-Jimenez M, Qin L
Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes.
Ebola virus: melatonin as a readily available treatment option.
2015-04 Anderson G, Maes M, Markus RP, Rodriguez M
There is currently an urgent need for a viable, cheap, and readily available treatment for the Ebola virus outbreak in West Africa. Here, it is proposed that melatonin may have significant utility in helping the management of this outbreak.
Melatonin, the Hormone of Darkness: From Sleep Promotion to Ebola Treatment.
2014-12 Masters A, Pandi-Perumal SR, Seixas A, Girardin JL, McFarlane SI
Melatonin is a hormone secreted by the enigmatic pineal gland in response to darkness, hence the name hormone of darkness. It has generated a great deal of interest as a therapeutic modality for various diseases particularly sleep disorders.
Ebola virus disease: potential use of melatonin as a treatment.
2014-11 Tan DX, Korkmaz A, Reiter RJ, Manchester LC
The purpose of this report is to emphasize the potential utility for the use of melatonin in the treatment of individuals who are infected with the Ebola virus.
Melatonin: its possible role in the management of viral infections – a brief review.
2013-10 Silvestri M, Rossi GA
Melatonin, a versatile molecule, is synthesized by the pineal gland but also by other organs, including gastrointestinal tract, retina, thymus, bone marrow, and by leukocytes.
On the free radical scavenging activities of melatonin’s metabolites, AFMK and AMK.
2013-04 Galano A, Tan DX, Reiter RJ
The reactions of N(1) -acetyl-N(2) -formyl-5-methoxykynuramine (AFMK) and N(1) -acetyl-5-methoxykynuramine (AMK) with (•) OH, (•) OOH, and •OOCCl3 radicals have been studied using the density functional theory.
Beneficial actions of melatonin in the management of viral infections: a new use for this “molecular handyman”?
2012-09 Boga JA, Coto-Montes A, Rosales-Corral SA, Tan DX, Reiter RJ
Melatonin (N-acetyl-5-methoxytryptamine) is a multifunctional signaling molecule that has a variety of important functions. Numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine.
Melatonin in bacterial and viral infections with focus on sepsis: a review.
2012-01 Srinivasan V, Mohamed M, Kato H
Melatonin is a versatile molecule, synthesized not only by the pineal gland, but also in small amounts by many other organs like retina, gastrointestinal tract, thymus, bone marrow, lymphocytes etc.
Fatigue in medical residents leads to reactivation of herpes virus latency.
2011-12 Uchakin PN, Parish DC, Dane FC, Uchakina ON, Scheetz AP, Agarwal NK, Smith BE
The main objective of this study was to detect fatigue-induced clinical symptoms of immune suppression in medical residents. Samples were collected from the subjects at rest, following the first night (low-stress), and the last night (high-stress) of night float.
Melatonin: a pleiotropic molecule regulating inflammation.
2010-12 Radogna F, Diederich M, Ghibelli L
Melatonin is a neurohormone produced by the pineal gland that regulates sleep and circadian functions. Melatonin also regulates inflammatory and immune processes acting as both an activator and inhibitor of these responses.
Melatonin: action as antioxidant and potential applications in human disease and aging.
2010-11 Bonnefont-Rousselot D, Collin F.
This review aims at describing the beneficial properties of melatonin related to its antioxidant effects. Oxidative stress, i.e., an imbalance between the production of reactive oxygen species and antioxidant defences, is involved in several pathological conditions such as cardiovascular or neurological disease, and in aging. Therefore, research for antioxidants has developed. However, classical antioxidants often failed to exhibit beneficial effects, especially in metabolic diseases.
Melatonin signaling and cell protection function.
2010-10 Luchetti F, Canonico B, Betti M, Arcangeletti M, Pilolli F, Piroddi M, Piroddi M, Canesi L, Papa S, Galli F
Besides its well-known regulatory role on circadian rhythm, the pineal gland hormone melatonin has other biological functions and a distinct metabolism in various cell types and peripheral tissues. In different tissues and organs, melatonin has been described to act as a paracrine and also as an intracrine and autocrine agent with overall homeostatic functions and pleiotropic effects that include cell protection and prosurvival factor.
Regression of herpes viral infection symptoms using melatonin and SB-73: comparison with Acyclovir.
2008-05 Nunes Oda S, Pereira Rde S
Infection with Herpes simplex virus type 1 (HSV-1) typically causes lesions of the mouth, face, skin, esophagus, or brain. Herpes simplex virus type 2 (HSV-2) usually causes infections of the genitals, rectum, skin, hands, or meninges.
One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species?
2007-01 Tan DX, Manchester LC, Terron MP, Flores LJ, Reiter RJ
Melatonin is a highly conserved molecule. Its presence can be traced back to ancient photosynthetic prokaryotes. A primitive and primary function of melatonin is that it acts as a receptor-independent free radical scavenger and a broad-spectrum antioxidant.
Antioxidant properties of the melatonin metabolite N1-acetyl-5-methoxykynuramine (AMK): scavenging of free radicals and prevention of protein destruction.
2003-12 Ressmeyer AR, Mayo JC, Zelosko V, Sáinz RM, Tan DX, Poeggeler B, Antolín I, Zsizsik BK, Reiter RJ, Hardeland R
In numerous experimental systems, the neurohormone melatonin has been shown to protect against oxidative stress, an effect which appears to be the result of a combination of different actions. In this study, we have investigated the possible contribution to radical scavenging by substituted kynuramines formed from melatonin via pyrrole ring cleavage.
Melatonin-immune system relationships.
2002-02 Guerrero JM , Reiter RJ
In this paper we review the historical milestones that first highlighted the existence of a relationship between melatonin and the immune system and we summarize data from experiments which correlate the rhythmic production of melatonin with the rhythmic activity of the immune system.