Official websites use. Share sensitive information only on official, secure websites. Licensee MDPI, Basel, Switzerland. Viral infections Mana World Sexy Boobs Blowjob a tectonic convulsion in the normophysiology of the hosts. The current coronavirus disease COVID 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. Melatonin is a systemic dealer that does not overlook any homeostasis disturbance, which consequently brings into play its cooperative triad, antioxidant, anti-inflammatory, and immune-stimulant backbone, to stop the infective cycle of SARS-CoV-2 or any other endogenous or exogenous threat. In COVID, the corporal propagation of SARS-CoV-2 involves an exacerbated oxidative activity and therefore the overproduction of great amounts of reactive oxygen and nitrogen species RONS. The endorsement of melatonin as a possible protective agent against the current pandemic is indirectly supported by its widely demonstrated beneficial role in preclinical and clinical studies of other respiratory diseases. In addition, focusing the therapeutic action on strengthening the host protection responses in critical phases of the infective cycle makes it likely that multi-tasking melatonin will provide multi-protection, maintaining its efficacy against the virus variants that are already emerging and will emerge as long as SARS-CoV-2 continues to circulate among us. Keywords: melatonin, SARS-CoV-2, safety, adjuvant therapy, mitochondria, inflammation, antioxidant, circadian rhythms, clinical trials. Recently, the rapid spread of new coronaviruses throughout the world has had a great impact on worldwide societal and economic development, besides it is being considered the most crucial global health disaster of the century [ 1 ]. The ongoing pandemic of coronavirus disease COVID caused by the severe acute respiratory syndrome coronavirus 2 SARC-CoV-2 has a plethora of presentations, drifting from asymptomatic to a severe state of the disease, with a wide variety of symptoms [ 2 ]. Globally, considering its high mortality and unexpected rapid spread, several groups of academia, industry, and the government sector are working together to develop an effective and safe treatment against COVID Besides pharmacological therapy, few scientific groups are working on non-pharmacological molecules that may reduce the risk of getting infected with COVID Melatonin plays an important role in the regulation of different physiological functions including free radical detoxification and immune system enhancing, besides exerting direct anti-inflammatory, anti-cancer, neuroprotective, cardiovascular, and anti-diabetic effects [ 34567 Mana World Sexy Boobs Blowjob, 8 ]. In the last months, moved by impotence in the face of the horror caused by COVID, numerous researchers have emphasized the therapeutic potential of melatonin [ 101112 ]. The pineal indoleamine is one of the molecules about which probably more pages have been written on its evolutionary origin, functionality, and applicability in clinical settings. As a result, its functional biology is one of the best-known, and we now realize that it goes far beyond the traditional role in controlling the circadian and seasonal cycles. On the contrary, melatonin is currently considered a universal cell protector with signaling actions in a myriad of biochemical processes essential for cell and tissue homeostasis [ 1314 ]. In this sense, among the plethora of mediations that melatonin carries out, the regulation of immunoinflammatory responses and the protection against oxidative damage are the focus of interest. The vast research around SARS-CoV-2 developed last year signals a double indirect contribution of melatonin-mediated responses to the natural defense against COVID morbimortality [ 19 ]. Additionally, it is equally conceivable that from strictly theoretical considerations based on the electronic structure of the molecule, the functionality of melatonin has been predicted, and docking simulations have suggested the potential efficacy of the indoleamine in the treatment of COVID [ 26 ], presuming its role as SARS-CoV-2 protease inhibitor [ 27 ]. On the empirical side, the observational study of a large COVID cohort showed that patients taking melatonin had a reduced risk of SARS-CoV-2 infection, even compared with those treated with potent angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, among others [ 25 ]. Likewise, individuals on melatonin treatment, along with other pharmacological, genre, ethnicity, and age features, have been positively discriminated as reduced-risk for COVID by a logistic regression algorithm over more than 11, people [ 28 ]. Moreover, the translational applicability of this molecule stands out over other therapy drug candidates to effectively and safely curtail the COVID pandemic [ 102529 ], as well as to enhance the immune response to vaccination [ 16303132 ]. Secondly, another plane in favor of melatonin in managing the immunopathology burden of COVID is directly envisaged from the predictable efficacy of its wide-ranging capacities. Later, hyper-inflammation by SARS-CoV-2 eventually leads to severe failure of the lungs, heart, and other peripheral organs, septic shock, and the irreversible perturbation of those whole biosystems that configure COVID pathogenesis and determines the prognosis of patients, often ending in death [ 3637 ]. However, at the same time, this immune-inflammatory status provides clues for the design of therapeutic approaches capable of adequately modulating the immune response. In this regard, melatonin can modulate innate and adaptive immunities, avoiding overreaction and the pathological escalation of the cytokine storm. In other words, the indoleamine helps to enhance host tolerance and Mana World Sexy Boobs Blowjob the viral cycle, preventing the systemic damage of tissues and organs [ 1838 ]. From the biological perspective, melatonin raises barriers against virus invasion and replication, so the infective strategy usually involves torpedoing its synthesis and signaling to hinder the crucial antioxidant, metabolic, and immune-modulatory actions played by the indoleamine in the defense of cellular homeostasis [ 193940 ]. In accordance with the above, as melatonin is produced endogenously and is also present in our diet, many researchers propose to supplement natural intakes with the indoleamine to emulate in COVID patients the benefits observed in entities with phenotypic similarities. The high tolerability of melatonin, even at high doses [ 4142 ], enhances the plausibility of efficient and safe melatonin-based COVID treatments. Only the increased risk of Mana World Sexy Boobs Blowjob high SARS-CoV-2 infectivity rate with age represents an immense public health challenge, since a potential population of more than 1. In anticipation of future scenarios of equal or greater complexity than COVID, the reinforcement of the host defense mechanisms provided by melatonin has the additional interest that a similar base treatment could be effective for other upcoming viral or microbial nosological entities associated with exacerbated immunoinflammation [ 18 ]. In sum, it is an ancient molecule at the forefront of future therapeutics. This is the promise that the urgent program of systematic investigation, which we want to claim herein, may put in our hands.
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