Can melatonin reduce the severity of COVID-19 pandemic?

Abstract

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. Children don't suffer from COVID-19 as much as their grandparents and have a much higher melatonin level. Bats are nocturnal animals possessing high levels of melatonin, which may contribute to their high anti-viral resistance. Viruses induce an explosion of inflammatory cytokines and reactive oxygen species, and melatonin is the best natural antioxidant that is lost with age. The programmed cell death coronaviruses cause, which can result in significant lung damage, is also inhibited by melatonin. Coronavirus causes inflammation in the lungs which requires inflammasome activity. Melatonin blocks these inflammasomes. General immunity is impaired by anxiety and sleep deprivation. Melatonin improves sleep habits, reduces anxiety and stimulates immunity. Fibrosis may be the most dangerous complication after COVID-19. Melatonin is known to prevent fibrosis. Mechanical ventilation may be necessary but yet imposes risks due to oxidative stress, which can be reduced by melatonin. Thus, by using the safe over-the-counter drug melatonin, we may be immediately able to prevent the development of severe disease symptoms in coronavirus patients, reduce the severity of their symptoms, and/or reduce the immuno-pathology of coronavirus infection on patients' health after the active phase of the infection is over. ARTICLE HISTORY

Implications of Oxidative Stress and Potential Role of Mitochondrial Dysfunction in COVID-19: Therapeutic Effects of Vitamin D

“…In this context, a vicious cycle of demethylation and augmented oxidative stress could increase susceptibility to SARS-CoV-2 infection [129]. Moreover, the antioxidant capacity is usually lost with age, and this pro-oxidative state associated with aging could be one of the reasons for which elderly people are more susceptible to being affected by SARS-CoV-2 infection [130][131][132].…”

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

“…It has been proven that there is a positive correlation between aging and the reduction of plasmatic melatonin, what may affect sleep quality as well as the suitable control of inflammatory processes and thus a higher risk of hyper-inflammation [66]. The beneficial effect of melatonin on acute lung injury states, sepsis and hyper-inflammatory processes caused by viruses, bacteria or radiation has been previously documented [67][68][69][70].…”

“…and, probably, antiviral mechanisms [64]. Another relevant topic is that the drug interaction of melatonin with the main drugs currently available can reduce the side effects such as renal damage and oxidative stress of the lopinavir/ ritonavir association, potentiate the antiviral response of ribavirin and reduce oedema when associated with methylprednisolone [66].…”

“…Melatonin could modulate inflammation by decreasing the activation of both NF-κB and inflammasomes NLRP3 (nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domaincontaining receptor 3). Therefore, there will be a reduction in cell membrane damage and the inflammatory release of cell content to the extracellular space [66]. The mechanism of action as inhibitor of NF-κB has not yet been fully clarified but it seems to involve reducing oxidative stress via NF-E2-related factor (Nrf2), reducing the binding ability of NF-κB via acetylation of the p50 subunit [71][72][73] and toll-like receptors (TLRs).…”

Exogenous melatonin as potential adjuvant in anti-SarsCov2 vaccines

“…In relation to viral diseases, MLT proved to counteract the infection in variety of models (Maestroni 2001) and recently it has been suggested to be of potential therapeutic value in reducing the severity of Covid-19 (Shneider et al 2020). As a matter of facts, Covid-19 may be remarkably severe in elderly males, i.e.…”