Viral Diseases

Medical Studies on Melatonin – Viral Diseases

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

Role of Melatonin on Virus-Induced Neuropathogenesis-A Concomitant Therapeutic Strategy to Understand SARS-CoV-2 Infection.

2021-01 Wongchitrat P, Shukla M, Sharma R, Govitrapong P, Reiter RJ

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.

Melatonin-Index as a biomarker for predicting the distribution of presymptomatic and asymptomatic SARS-CoV-2 carriers

2021-01 Fernandes PA, Kinker GS, Navarro BV, Jardim VC, Ribeiro-Paz ED, Córdoba-Moreno MO, Santos-Silva D, Muxel SM, Fujita A,  Moraes C, Nakaya HI, Buckeridge MS, Markus RP

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.

A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19

2020-10 Zhou Y, Hou Y, Shen J, Kallianpur A, Zein J, Culver DA, Farha S, Comhair S, Fiocchi C, Gack MU, Mehra R, Stappenbeck T, Chan T, Eng C, Jung JU, Jehi L, Erzurum S, Cheng F

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

2020-10 Ramlall V, Zucker J, Tatonetti N

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

2020-09 Tan DX, Hardeland R

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

2020-09 El-Missiry MA, El-Missiry ZMA, Othman AI

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

2020-08 Al-Zaqri N, Pooventhiran T, Alsalme A, Warad I, John AM, Thomas R

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.

Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment

2020-08 Martín Giménez VM, Inserra F, Tajer CD, Mariani J, Ferder L, Reiter RJ, Manucha W

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.

Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis

2020-07 Hazra S, Chaudhuri AG, Tiwary BK, Chakrabartia N

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

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.

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 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: 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.

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.

Scroll to Top