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
A Review of the Potential Effects of Melatonin in Compromised Mitochondrial Redox Activities in Elderly Patients With COVID-19
Melatonin, an endogenous indoleamine, is an antioxidant and anti-inflammatory molecule widely distributed in the body. It efficiently regulates pro-inflammatory and anti-inflammatory cytokines under various pathophysiological conditions. The melatonin rhythm, which is strongly associated with oxidative lesions and mitochondrial dysfunction, is also observed during the biological process of aging. Melatonin levels decline considerably with age and are related to numerous age-related illnesses.
Does melatonin reduce mortality in COVID-19?
Coronaviruses (CoVs) usually affect the respiratory system of mammals causing mild to severe infections. In the past two decades pathogenic human CoVs with high morbidity and mortality such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) emerged from animal reservoirs.
Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels
COVID-19 is a complex disease with short- and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. Invasion of the brain by SARS-CoV-2 has been observed in humans and is postulated to be involved in post-COVID state. Brain infection is particularly pronounced in the K18-hACE2 mouse model of COVID-19. Prevention of brain infection in the acute phase of the disease might thus be of therapeutic relevance to prevent long-lasting symptoms of COVID-19.
Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia
Despite intense investigation, the pathogenesis of COVID-19 and the newly defined long COVID-19 syndrome are not fully understood. Increasing evidence has been provided of metabolic alterations characterizing this group of disorders, with particular relevance of an activated tryptophan/kynurenine pathway as described in this review.
Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection
Numerous pharmaceutical drugs have been repurposed for use as treatments for COVID-19 disease. These drugs have not consistently demonstrated high efficacy in preventing or treating this serious condition and all have side effects to differing degrees. We encourage the continued consideration of the use of the antioxidant and anti-inflammatory agent, melatonin, as a countermeasure to a SARS-CoV-2 infection.
“LONG COVID”-A hypothesis for understanding the biological basis and pharmacological treatment strategy
Infection of humans with SARS-CoV-2 virus causes a disease known colloquially as "COVID-19" with symptoms ranging from asymptomatic to severe pneumonia.
The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients
This study aimed to determine the effect of melatonin on thrombosis, sepsis, and mortality rate in adult patients with severe coronavirus infection (COVID-19).
Melatonin reduces the mortality of severely-infected COVID-19 patients
SARS-CoV-2 has ravaged the population of the world for two years. Scientists have not yet identified an effective therapy to reduce the mortality of severe COVID-19 patients. In a single-center, open-label, randomized clinical trial, it was observed that melatonin treatment lowered the mortality rate by 93% in severely-infected COVID-19 patients compared with the control group (see below). This is seemingly the first report to show such a huge mortality reduction in severe COVID-19 infected individuals with a simple treatment. If this observation is confirmed by more rigorous clinical trials, melatonin could become an important weapon to combat this pandemic.
The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy
Viral infections constitute a tectonic convulsion in the normophysiology of the hosts. The current coronavirus disease 2019 (COVID-19) pandemic is not an exception, and therefore the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, like any other invading microbe, enacts a generalized immune response once the virus contacts the body.
A preliminar study of a neuroimmune regimen with low-dose angiotensin 1-7 plus melatonin to improve the safety of covid 19 vaccine
In experimental conditions, it has been demonstrated that vaccine efficacy and the toxicity is depending on cytokine-induced immunoinflammatory response, and that they may be modulate through a neuroimmune approach, which neuroendocrine agents, such as the pineal hormone melatonin (MLT) and the enzymatic product of ACE2, the angiotensin 1-7 (Ang 1-7). On these bases, a preliminary study was planned to evaluate the influence of an oral peri-vaccination regimen with MLT plus Ang 1-7 on the subjective safety of Covid19 Pfizer-BioNTech (PF) and AstraZeneca (AZ) vaccines.
Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial
Melatonin has been known as an anti-inflammatory agent and immune modulator that may address progressive pathophysiology of coronavirus disease 2019 (COVID-19). Aim of the study. To evaluate the clinical efficacy of adjuvant, use of melatonin in patients with COVID-19.
Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment
Coronavirus (SARS-CoV-2) is spreading rapidly in the world and is still taking a heavy toll. Studies show that cytokine storms and imbalances in T-helper (Th)1/Th2 play a significant role in most acute cases of the disease.
Inflammation, immunity and potential target therapy of SARS-COV-2: A total scale analysis review
Coronavirus disease-19 (COVID-19) is a complex disease that causes illness ranging from mild to severe respiratory problems. It is caused by a novel coronavirus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) that is an enveloped positive-sense single-stranded RNA (+ssRNA) virus belongs to coronavirus CoV family.
SARS-CoV-2 and other coronaviruses negatively influence mitochondrial quality control: beneficial effects of melatonin
Coronaviruses (CoVs) are a group of single stranded RNA viruses, of which some of them such as SARS-CoV, MERS-CoV, and SARS-CoV-2 are associated with deadly worldwide human diseases. Coronavirus disease-2019 (COVID-19), a condition caused by SARS-CoV-2, results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with high mortality in the elderly and in people with underlying comorbidities.
Role of Melatonin on Virus-Induced Neuropathogenesis-A Concomitant Therapeutic Strategy to Understand SARS-CoV-2 Infection.
Viral infections may cause neurological disorders by directly inducing oxidative stress and interrupting immune system function, both of which contribute to neuronal death. Several reports have described the neurological manifestations in Covid-19 patients where, in severe cases of the infection, brain inflammation and encephalitis are common.
Relationship Between Sleep Quality and the Psychological Status of Patients Hospitalised with COVID-19
We explored the sleep quality of patients who required mental health and clinical interventions in our hospital after being diagnosed with COVID-19.
Melatonin-Index as a biomarker for predicting the distribution of presymptomatic and asymptomatic SARS-CoV-2 carriers
The pandemic dissemination of the SARS-CoV-2 led, on the one hand, to a worldwide effort to develop mechanistic-based therapeutics and vaccines, and on the other hand, the searching for determining the spreaders and the mechanisms of transmission. Melatonin, a multitask molecule, orchestrates defense responses by allowing the proper mounting, duration, and magnitude of innate immune responses.
An urgent proposal for the immediate use of melatonin as an adjuvant to anti- SARS-CoV-2 vaccination
Competition among pharmaceutical companies to develop safe and effective vaccines against SARS-CoV-2 is high. However, based on the prior experience with the influenza vaccine, up to 50% in lack of effectiveness would be found among healthy adults receiving effective vaccines against SARS-CoV-2.
Can Melatonin Be a Potential “Silver Bullet” in Treating COVID-19 Patients?
The therapeutic potential of melatonin as a chronobiotic cytoprotective agent to counteract the consequences of COVID-19 infections has been advocated. Because of its wide-ranging effects as an antioxidant, anti-inflammatory, and immunomodulatory compound, melatonin could be unique in impairing the consequences of SARS-CoV-2 infection.
A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19
The global Coronavirus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of co-existing medical conditions while the underlying mechanisms remain unclear. Furthermore, there are no proven effective therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, diseases manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations.
Melatonin is significantly associated with survival of intubated COVID-19 patients
Respiratory distress requiring intubation is the most serious complication associated with coronavirus disease 2019 (COVID-19). In this retrospective study, we used survival analysis to determine whether or not mortality following intubation was associated with hormone exposure in patients treated at New York Presbyterian/ Columbia University Irving Medical Center. Here, we report the overall hazards ratio for each hormone for exposure before and after intubation for intubated and mechanically ventilated patients.
Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19
Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen's spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution.
Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of Covid-19
Coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a newly discovered highly pathogenic virus that was declared pandemic in March 2020 by the World Health Organization. The virus affects the respiratory system, produces an inflammatory storm that causes lung damage and respiratory dysfunction. It infects humans of all ages.
Structural and physico-chemical evaluation of melatonin and its solution-state excited properties, with emphasis on its binding with novel coronavirus proteins
Melatonin is a natural hormone from the pineal gland that regulates the sleep-wake cycle. We examined the structure and physico-chemical properties of melatonin using electronic structure methods and molecular-mechanics tools. Density functional theory (DFT) was used to optimise the ground-state geometry of the molecule from frontier molecular orbitals, which were analysed using the B3LYP functional.
Coronavirus Disease 2019 (COVID-19) and Its Neuroinvasive Capacity: Is It Time for Melatonin?
The world faces an exceptional new public health concern caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequently termed the coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO).
Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment
COVID-19 pandemic has a high mortality rate and is affecting practically the entire world population. The leading cause of death is severe acute respiratory syndrome as a consequence of exacerbated inflammatory response accompanied by uncontrolled oxidative stress as well as the inflammatory reaction at the lung level.
Crosstalk between endoplasmic reticulum stress and anti-viral activities: A novel therapeutic target for COVID-19
The outbreak of COVID-19 caused by 2019-nCov/SARS-CoV-2 has become a pandemic with an urgent need for understanding the mechanisms and identifying a treatment.
Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis
The molecular pathogenesis of COVID-19 is similar to other coronavirus (CoV) infections viz. severe acute respiratory syndrome (SARS) in human. Due to scarcity of the suitable treatment strategy, the present study was undertaken to explore host protein(s) targeted by potent repurposed drug(s) in COVID-19.
Plasticity of glucose metabolism in activated immune cells: advantages for melatonin inhibition of COVID-19 disease
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?
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
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
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
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
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.
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.
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?
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.
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”.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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”?
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.
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.
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.
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.
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.
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.
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?
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.
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.
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.