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1.
Molecules ; 27(15)2022 Jul 28.
Article in English | MEDLINE | ID: covidwho-1994115

ABSTRACT

Carotenoid succinates were synthesized from hydroxy carotenoids and were coupled to a commercially available derivative of melatonin via amide bond for producing more powerful anti-oxidants and yet new hybrid lipophilic bifunctional molecules with additional therapeutic effects. The coupling reactions produced conjugates in acceptable to good yields. Succinylation increased the water solubility of the carotenoids, while the conjugation with melatonin resulted in more lipophilic derivatives. The conjugates showed self-assembly in aqueous medium and yielded relatively stable colloidal solutions in phosphate-buffered saline. Antioxidant behavior was measured with ABTS and the FRAP methods for the carotenoids, the carotenoid succinates, and the conjugates with melatonin. A strong dependence on the quality of the solvent was observed. TEAC values of the new derivatives in phosphate-buffered saline were found to be comparable to or higher than those of parent carotenoids, however, synergism was observed only in FRAP assays.


Subject(s)
Antioxidants , Melatonin , Antioxidants/chemistry , Carotenoids/chemistry , Phosphates , Succinates
2.
J Am Board Fam Med ; 35(4): 695-707, 2022.
Article in English | MEDLINE | ID: covidwho-1963338

ABSTRACT

This study aimed to help determine the effect of dietary supplements on symptom course and quality of life in patients with mild-to-moderate COVID-19 infection. DESIGN: We modified the Wisconsin Upper Respiratory Symptom Survey (WURSS) to conduct a 3 arm, parallel, randomized, double-blind, placebo-controlled trial, enrolling patients with mild-to-moderate symptoms of COVID-19 infection. Patients took placebo (n = 34), vitamin C 1000 mg (n = 32), or melatonin 10 mg (n = 32) orally for 14 days. OUTCOMES: Ninety Eight (98 out of 104 recruited; mean age = 52 years) patients completed the study. Outcomes were calculated as differences from baseline scores on each of 2 WURSS-derived surveys and analyzed using a spline regression analysis. Regarding symptom progression, those patients taking placebo and vitamin C progressed at the same rate. When compared with those taking placebo (coefficient = -1.09 (95% confidence interval [CI] = -1.39 to -0.8) the group taking melatonin had a faster resolution of symptoms (coefficient = -0.63 [95% CI -1.02 to -0.21] P = .003). By day 14 all 3 groups had reached plateau.Quality-of-life impact analysis demonstrated that the group taking vitamin C improved at the same rate as the group taking placebo (coefficient = -0.71 (95% CI = -1.11 to -0.3)). The group taking melatonin (coefficient = -1.16 (95% CI = -1.75 to - 0.57) P < .005) had a faster improvement in quality-of-life. By day 14 all 3 groups had reached plateau. CONCLUSION: Vitamin C 1000 mg once daily has no effect on disease progression. Melatonin 10 mg daily may have a statistically significant effect but it is unclear if this represents a clinically significant benefit to those with mild-to-moderate symptoms of COVID-19 infection. Further study is warranted.


Subject(s)
COVID-19 , Melatonin , Ascorbic Acid/therapeutic use , COVID-19/drug therapy , Double-Blind Method , Humans , Melatonin/adverse effects , Melatonin/therapeutic use , Middle Aged , Quality of Life , Vitamins/therapeutic use
3.
Int J Mol Sci ; 23(15)2022 Jul 23.
Article in English | MEDLINE | ID: covidwho-1957346

ABSTRACT

The relentless, protracted evolution of the SARS-CoV-2 virus imposes tremendous pressure on herd immunity and demands versatile adaptations by the human host genome to counter transcriptomic and epitranscriptomic alterations associated with a wide range of short- and long-term manifestations during acute infection and post-acute recovery, respectively. To promote viral replication during active infection and viral persistence, the SARS-CoV-2 envelope protein regulates host cell microenvironment including pH and ion concentrations to maintain a high oxidative environment that supports template switching, causing extensive mitochondrial damage and activation of pro-inflammatory cytokine signaling cascades. Oxidative stress and mitochondrial distress induce dynamic changes to both the host and viral RNA m6A methylome, and can trigger the derepression of long interspersed nuclear element 1 (LINE1), resulting in global hypomethylation, epigenetic changes, and genomic instability. The timely application of melatonin during early infection enhances host innate antiviral immune responses by preventing the formation of "viral factories" by nucleocapsid liquid-liquid phase separation that effectively blockades viral genome transcription and packaging, the disassembly of stress granules, and the sequestration of DEAD-box RNA helicases, including DDX3X, vital to immune signaling. Melatonin prevents membrane depolarization and protects cristae morphology to suppress glycolysis via antioxidant-dependent and -independent mechanisms. By restraining the derepression of LINE1 via multifaceted strategies, and maintaining the balance in m6A RNA modifications, melatonin could be the quintessential ancient molecule that significantly influences the outcome of the constant struggle between virus and host to gain transcriptomic and epitranscriptomic dominance over the host genome during acute infection and PASC.


Subject(s)
COVID-19 , Melatonin , Host-Pathogen Interactions , Humans , RNA, Viral , SARS-CoV-2 , Virus Replication
4.
J Bras Pneumol ; 48(3): e20220191, 2022 07 08.
Article in English, Portuguese | MEDLINE | ID: covidwho-1935014
5.
Cell Mol Life Sci ; 79(7): 361, 2022 Jun 13.
Article in English | MEDLINE | ID: covidwho-1888837

ABSTRACT

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. We previously showed that melatonin or two prescribed structural analogs, agomelatine and ramelteon delay the onset of severe clinical symptoms and improve survival of SARS-CoV-2-infected K18-hACE2 mice. Here, we show that treatment of K18-hACE2 mice with melatonin and two melatonin-derived marketed drugs, agomelatine and ramelteon, prevents SARS-CoV-2 entry in the brain, thereby reducing virus-induced damage of small cerebral vessels, immune cell infiltration and brain inflammation. Molecular modeling analyses complemented by experimental studies in cells showed that SARS-CoV-2 entry in endothelial cells is prevented by melatonin binding to an allosteric-binding site on human angiotensin-converting enzyme 2 (ACE2), thus interfering with ACE2 function as an entry receptor for SARS-CoV-2. Our findings open new perspectives for the repurposing of melatonergic drugs and its clinically used analogs in the prevention of brain infection by SARS-CoV-2 and COVID-19-related long-term neurological symptoms.


Subject(s)
COVID-19 , Melatonin , Angiotensin-Converting Enzyme 2 , Animals , Brain/metabolism , COVID-19/drug therapy , Endothelial Cells/metabolism , Melatonin/pharmacology , Melatonin/therapeutic use , Mice , Mice, Transgenic , Peptidyl-Dipeptidase A , SARS-CoV-2
6.
Mol Biol Rep ; 49(5): 4061-4068, 2022 May.
Article in English | MEDLINE | ID: covidwho-1877913

ABSTRACT

The omicron variant (B.529) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late 2021, caused panic worldwide due to its contagiousness and multiple mutations in the spike protein compared to the Delta variant (B.617.2). There is currently no specific antiviral available to treat Coronavirus disease 2019 (COVID-19). However, studies on neutralizing monoclonal antibodies (mAb) developed to fight COVID-19 are growing and gaining traction. REGN-COV2 (Regeneron or imdevimab-casirivimab combination), which has been shown in recent studies to be less affected by Omicron's RBD (receptor binding domain) mutations among other mAb cocktails, plays an important role in adjuvant therapy against COVID-19. On the other hand, it is known that melatonin, which has antioxidant and immunomodulatory effects, can prevent a possible cytokine storm, and other severe symptoms that may develop in the event of viral invasion. Along with all these findings, we believe it is crucial to evaluate the use of melatonin with REGN-COV2, a cocktail of mAbs, as an adjuvant in the treatment and prevention of COVID-19, particularly in immunocompromised and elderly patients.


Subject(s)
Antineoplastic Agents, Immunological , COVID-19 , Melatonin , Aged , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , COVID-19/drug therapy , Drug Combinations , Humans , Melatonin/pharmacology , Melatonin/therapeutic use , SARS-CoV-2
8.
BMJ Open ; 12(5): e055716, 2022 05 10.
Article in English | MEDLINE | ID: covidwho-1832449

ABSTRACT

BACKGROUND: During adolescence, sleep and circadian timing shift later, contributing to restricted sleep duration and irregular sleep-wake patterns. The association of these developmental changes in sleep and circadian timing with cognitive functioning, and consequently academic outcomes, has not been examined prospectively. The role of ambient light exposure in these developmental changes is also not well understood. Here, we describe the protocol for the Circadian Light in Adolescence, Sleep and School (CLASS) Study that will use a longitudinal design to examine the associations of sleep-wake timing, circadian timing and light exposure with academic performance and sleepiness during a critical stage of development. We also describe protocol adaptations to enable remote data collection when required during the COVID-19 pandemic. METHODS: Approximately 220 healthy adolescents aged 12-13 years (school Year 7) will be recruited from the general community in Melbourne, Australia. Participants will be monitored at five 6 monthly time points over 2 years. Sleep and light exposure will be assessed for 2 weeks during the school term, every 6 months, along with self-report questionnaires of daytime sleepiness. Circadian phase will be measured via dim light melatonin onset once each year. Academic performance will be measured via national standardised testing (National Assessment Program-Literacy and Numeracy) and the Wechsler Individual Achievement Test-Australian and New Zealand Standardised Third Edition in school Years 7 and 9. Secondary outcomes, including symptoms of depression, anxiety and sleep disorders, will be measured via questionnaires. DISCUSSION: The CLASS Study will enable a comprehensive longitudinal assessment of changes in sleep-wake timing, circadian phase, light exposure and academic performance across a key developmental stage in adolescence. Findings may inform policies and intervention strategies for secondary school-aged adolescents. ETHICS AND DISSEMINATION: Ethical approval was obtained by the Monash University Human Research Ethics Committee and the Victorian Department of Education. Dissemination plans include scientific publications, scientific conferences, via stakeholders including schools and media. STUDY DATES: Recruitment occurred between October 2019 and September 2021, data collection from 2019 to 2023.


Subject(s)
Academic Performance , COVID-19 , Melatonin , Adolescent , Australia , COVID-19/epidemiology , Child , Circadian Rhythm , Humans , Pandemics , Prospective Studies , Schools , Sleep
9.
Clin Cardiol ; 45(4): 417-426, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1797946

ABSTRACT

BACKGROUND: Melatonin, the major secretion of the pineal gland, has beneficial effects on the cardiovascular system and might advantage heart failure with reduced ejection fraction (HFrEF) by attenuating the effects of the renin-angiotensin-aldosterone and sympathetic system on the heart besides its antioxidant and anti-inflammatory effects. HYPOTHESIS: We hypothesized that oral melatonin might improve echocardiographic parameters, serum biomarkers, and a composite clinical outcome (including quality of life, hospitalization, and mortality) in patients with HFrEF. METHODS: A placebo-controlled double-blinded randomized clinical trial was conducted on patients with stable HFrEF. The intervention was 10 mg melatonin or placebo tablets administered every night for 24 weeks. Echocardiography and measurements of N-terminal pro-B-type natriuretic peptide (NT-Pro BNP), high-sensitivity C-reactive protein, lipid profile, and psychological parameters were done at baseline and after 24 weeks. RESULTS: Overall, 92 patients were recruited, and 85 completed the study (melatonin: 42, placebo: 43). Serum NT-Pro BNP decreased significantly in the melatonin compared with the placebo group (estimated marginal means for difference [95% confidence interval]: 111.0 [6.2-215.7], p = .044). Moreover, the melatonin group had a significantly better clinical outcome (0.93 [0.18-1.69], p = .017), quality of life (5.8 [0.9-12.5], p = .037), and New York Heart Association class (odds ratio: 12.9 [1.6-102.4]; p = .015) at the end of the trial. Other studied outcomes were not significantly different between groups. CONCLUSIONS: Oral melatonin decreased NT-Pro BNP and improved the quality of life in patients with HFrEF. Thus it might be a beneficial supplement in HFrEF.


Subject(s)
Heart Failure , Melatonin , Dietary Supplements , Heart Failure/diagnosis , Heart Failure/drug therapy , Humans , Melatonin/adverse effects , Natriuretic Peptide, Brain , Peptide Fragments , Quality of Life , Stroke Volume
10.
Vertex ; XXXIII(155): 13-24, 2022 Mar.
Article in Spanish | MEDLINE | ID: covidwho-1791217

ABSTRACT

INTRODUCTION: Melatonin is a safe medication with multiple uses in sleep medicine for the treatment of circadian rhythm disorders, insomnia, and REM sleep behavior disorder. In view that melatonin has been recommended as an adjuvant treatment in COVID-19 pandemic mainly due to its anti-inflammatory properties, the objective of the present study was to evaluate the history of COVID-19 infection and the requirement of hospitalization in a group of adult patients previously treated with melatonin for various sleep disorders. MATERIAL AND METHODS: This is a retrospective cross-sectional study of data from a closed population of 110 adult patients at a University Hospital treated with melatonin for various sleep disorders, analyzed until the onset of COVID-19 pandemic. Demographic and melatonin-related variables (dose, treatment time) were analyzed and were reevaluated during the pandemic period, by scheduled tele-consultation regarding diagnosis, hospitalization requirements, variables related to COVID-19 infection prior to specific vaccination. Categorical variables were described as relative and absolute frequencies. RESULTS: N = 110 patients. Age range = 40- 96 years (mean = 71 years ± 9.9), older adults > 65 years: N =87 (79,1%). COVID-19 infection was recorded in 15 patients (13.5%) requiring hospitalization in 5 of those infected, only one of them with severe pneumonia. There were no deaths due to COVID-19. There were no differences between infected vs. uninfected in age (p = 0.74), body mass index (p = 0.65) or melatonin dose (p = 0.10).The melatonin dose range was 3-150 mg / day (mean = 46.33 ± 34.1), older adults receiving a mean dose of 50,3 ± 35,6.The 75.5% of the patients were treated for at least 12 months with melatonin. CONCLUSION: We found that 13.5% of patients previously treated with melatonin for various sleep disorders were infected by COVID-19, requiring hospitalization with subsequent medical discharge one third of them. According to national records the lethality rate in older adults in August 2020 was 10.5%. No patient treated with melatonin died for this cause in this sample. We did not find statistically significant differences in terms of indicated melatonin dose, age or body mass index, when comparing those infected with those not infected. The patients in general were mostly older adults, treated with a mean dose greater than 40 mg / day of melatonin for various sleep disorders, mainly for complaints of insomnia, for more than 12 months. The results are consistent with a possible preventive effect of melatonin in the COVID-19 pandemic.


Subject(s)
COVID-19 , Melatonin , Sleep Initiation and Maintenance Disorders , Sleep Wake Disorders , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Cross-Sectional Studies , Humans , Melatonin/therapeutic use , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2 , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Wake Disorders/drug therapy , Sleep Wake Disorders/epidemiology
11.
J Med Virol ; 94(5): 2102-2107, 2022 05.
Article in English | MEDLINE | ID: covidwho-1777583

ABSTRACT

This study investigated the effect of melatonin on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). We searched PubMed, the Web of Science, the Cochrane Library, Ovid MEDLINE, and Clinicaltrials.gov for randomized controlled trials (RCTs) published before September 11, 2021. Only RCTs that compared the clinical efficacy of melatonin with a placebo in the treatment of patients with COVID-19 were included. The primary outcome measure was the clinical recovery rate. We included three RCTs in this meta-analysis. Melatonin 3 mg three times daily was administered in one RCT, and 3 or 6 mg daily before bedtime in the other two trials. Treatment duration was 14 days in two RCTs and 7 days in one trial. The clinical recovery rates were 94.2% (81/86) and 82.4% (70/85) in the melatonin and control groups, respectively. Overall, patients receiving melatonin had a higher clinical recovery rate than did the controls (odds ratio [OR]: 3.67; 95% CI: 1.21-11.12; I2 = 0%, p = 0.02). The risk of intensive care unit admission was numerically lower in the melatonin group than in the control group (8.3% [6/72] vs. 17.6% [12/68], OR: 0.45; 95% CI: 0.16-1.25; I2 = 0%, p = 0.13), and the risk of mortality was numerically lower in the melatonin group than in the control group (1.4% [1/72] vs. 4.4% [3/68], OR: 0.32; 95% CI: 0.03-3.18; I2 = 0%, p = 0.33). In conclusion, melatonin may help improve the clinical outcomes of patients with COVID-19.


Subject(s)
COVID-19 , Melatonin , COVID-19/drug therapy , Humans , Melatonin/therapeutic use , Randomized Controlled Trials as Topic , Respiration, Artificial , SARS-CoV-2
13.
Cell Mol Life Sci ; 79(3): 143, 2022 Feb 20.
Article in English | MEDLINE | ID: covidwho-1701908

ABSTRACT

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. More than 140 scientific publications have identified melatonin as a likely useful agent to treat this disease. Moreover, the publications cited provide the rationale for the use of melatonin as a prophylactic agent against this condition. Melatonin has pan-antiviral effects and it diminishes the severity of viral infections and reduces the death of animals infected with numerous different viruses, including three different coronaviruses. Network analyses, which compared drugs used to treat SARS-CoV-2 in humans, also predicted that melatonin would be the most effective agent for preventing/treating COVID-19. Finally, when seriously infected COVID-19 patients were treated with melatonin, either alone or in combination with other medications, these treatments reduced the severity of infection, lowered the death rate, and shortened the duration of hospitalization. Melatonin's ability to arrest SARS-CoV-2 infections may reduce health care exhaustion by limiting the need for hospitalization. Importantly, melatonin has a high safety profile over a wide range of doses and lacks significant toxicity. Some molecular processes by which melatonin resists a SARS-CoV-2 infection are summarized. The authors believe that all available, potentially beneficial drugs, including melatonin, that lack toxicity should be used in pandemics such as that caused by SARS-CoV-2.


Subject(s)
Antioxidants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Melatonin/therapeutic use , SARS-CoV-2/drug effects , COVID-19/virology , Humans
15.
Chemosphere ; 295: 133869, 2022 May.
Article in English | MEDLINE | ID: covidwho-1664752

ABSTRACT

Melatonin (MLT), a hormone related to the regulation of brain functions, is directly related to sleep quality and is considered to be a possible adjuvant therapy for patients needing hospitalization for coronavirus disease 2019 pneumonia, and accurate measurement of MLT is crucial. Herein, a new, highly sensitive, and easy operation fluorescent probe was provided based on Zr metal-organic framework encapsulation into the molecularly imprinted polymer (MOF@MIP). By combining unique properties of MIP and fluorescent MOF, selectivity and operation of the applied method were significantly improved. Different characterization methods, such as XRD, FT-IR, and FE-SEM, were used to confirm the synthesis reliability. MOF@MIP was successfully used for the precise identification and ultrasensitive detection for trace amounts of MLT. The detection mechanism for the analytical system is based on the ''turn-on'' fluorescence (FL) signal in 404 nm. The findings proved that it is possible to detect trace amounts of MLT in real samples including grape, cherry, and sour cherry juice. The linear range and the limit of detection (LOD) for trace amounts of MLT were obtained as 1-100 ng/mL and 0.18 ng/mL, respectively.


Subject(s)
COVID-19 , Melatonin , Molecular Imprinting , Humans , Limit of Detection , Reproducibility of Results , SARS-CoV-2 , Spectroscopy, Fourier Transform Infrared
16.
Signal Transduct Target Ther ; 7(1): 29, 2022 01 28.
Article in English | MEDLINE | ID: covidwho-1655546

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted on mink farms between minks and humans in many countries. However, the systemic pathological features of SARS-CoV-2-infected minks are mostly unknown. Here, we demonstrated that minks were largely permissive to SARS-CoV-2, characterized by severe and diffuse alveolar damage, and lasted at least 14 days post inoculation (dpi). We first reported that infected minks displayed multiple organ-system lesions accompanied by an increased inflammatory response and widespread viral distribution in the cardiovascular, hepatobiliary, urinary, endocrine, digestive, and immune systems. The viral protein partially co-localized with activated Mac-2+ macrophages throughout the body. Moreover, we first found that the alterations in lipids and metabolites were correlated with the histological lesions in infected minks, especially at 6 dpi, and were similar to that of patients with severe and fatal COVID-19. Particularly, altered metabolic pathways, abnormal digestion, and absorption of vitamins, lipids, cholesterol, steroids, amino acids, and proteins, consistent with hepatic dysfunction, highlight metabolic and immune dysregulation. Enriched kynurenine in infected minks contributed to significant activation of the kynurenine pathway and was related to macrophage activation. Melatonin, which has significant anti-inflammatory and immunomodulating effects, was significantly downregulated at 6 dpi and displayed potential as a targeted medicine. Our data first illustrate systematic analyses of infected minks to recapitulate those observations in severe and fetal COVID-19 patients, delineating a useful animal model to mimic SARS-CoV-2-induced systematic and severe pathophysiological features and provide a reliable tool for the development of effective and targeted treatment strategies, vaccine research, and potential biomarkers.


Subject(s)
COVID-19/metabolism , Lung/metabolism , Macrophages, Alveolar/metabolism , Metabolome , Mink/virology , SARS-CoV-2/metabolism , Amino Acids/metabolism , Animals , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/genetics , COVID-19/pathology , Disease Models, Animal , Female , Humans , Lung/pathology , Lung/virology , Macrophages, Alveolar/pathology , Macrophages, Alveolar/virology , Melatonin/metabolism , Metabolic Networks and Pathways/genetics , Molecular Targeted Therapy/methods , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Sterols/metabolism , Virulence , Virus Replication/genetics
17.
Life Sci ; 294: 120368, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1654900

ABSTRACT

The fear of SARS-CoV-2 infection is due to its high mortality related to seasonal flu. To date, few medicines have been developed to significantly reduce the mortality of the severe COVID-19 patients, especially those requiring tracheal intubation. The severity and mortality of SARS-CoV-2 infection not only depend on the viral virulence, but are primarily determined by the cytokine storm and the destructive inflammation driven by the host immune reaction. Thus, to target the host immune response might be a better strategy to combat this pandemic. Melatonin is a molecule with multiple activities on a virus infection. These include that it downregulates the overreaction of innate immune response to suppress inflammation, promotes the adaptive immune reaction to enhance antibody formation, inhibits the entrance of the virus into the cell as well as limits its replication. These render it a potentially excellent candidate for treatment of the severe COVID-19 cases. Several clinical trials have confirmed that melatonin when added to the conventional therapy significantly reduces the mortality of the severe COVID-19 patients. The cost of melatonin is a small fraction of those medications approved by FDA for emergency use to treat COVID-19. Because of its self-administered, low cost and high safety margin, melatonin could be made available to every country in the world at an affordable cost. We recommend melatonin be used to treat severe COVID-19 patients with the intent of reducing mortality. If successful, it would make the SARS-CoV-2 pandemic less fearful and help to return life back to normalcy.


Subject(s)
COVID-19/drug therapy , Melatonin/therapeutic use , SARS-CoV-2 , Anti-Inflammatory Agents , Antioxidants , COVID-19/immunology , COVID-19/mortality , Cytokine Release Syndrome/drug therapy , Humans , Immunity, Innate/drug effects , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Virus Replication/drug effects
18.
Med Sci (Paris) ; 38(1): 89-95, 2022 Jan.
Article in French | MEDLINE | ID: covidwho-1642032

ABSTRACT

Melatonin is a naturally occurring molecule derived from tryptophan. Melatonin is a key player in relaying the circadian rhythm between our environment and our body. It has also a key role in rhythming the seasons (more production during long nights and less during short ones) as well as in the reproduction cycles of the mammals. Melatonin is often and surprisingly presented as a molecule with multiple therapeutic properties that can fix (or help to fix) many health issues, such as diseases (cancer, ageing, virus-induced affections including COVID-19, etc…) or toxicological situations (metals, venoms, chemical such as adriamycin [doxorubicin], methotrexate or paclitaxel). The mechanistics behind those wonders is still missing and this is puzzling. In the present commentary, the main well-established biological properties are presented and briefly discussed with the aim of delineating the borders between facts and wishful thinking.


TITLE: Mélatonine - Petit précis à l'usage des trop enthousiastes. ABSTRACT: La mélatonine est une molécule naturelle dérivée du tryptophane. Son rôle est de servir de relai entre la rythmicité jour/nuit et notre corps. Elle sert donc de marqueur circadien : concentration haute pendant la nuit et basse pendant la journée. Elle sert aussi de marque saisonnière : plus les nuits sont longues et plus longuement elle est produite (et vice-versa), ce qui a un rôle primordial dans les cycles reproductifs des animaux. Mais elle est aussi affublée de multiples propriétés thérapeutiques concernant la plupart des maladies humaines, du cancer à la COVID-19 en passant par l'infection par le virus Ebola, ainsi que de capacités thérapeutiques vis-à-vis de multiples toxicités (métaux, venins, produits chimiques comme l'adriamycine [doxorubicine], le méthotrexate ou le paclitaxel). Alors que l'enthousiasme à propos de cette molécule est troublant, l'assise scientifique de ces descriptions est dans le meilleur des cas faible et dans la plupart des cas, inexistante. Dans ce commentaire, les données scientifiques bien établies liées à la mélatonine sont résumées et brièvement discutées, en tâchant de redessiner les limites entre ce qui est connu et bien établi et ce qui reste du domaine du fantasme.


Subject(s)
Circadian Rhythm/drug effects , Communication , Melatonin/pharmacology , Melatonin/physiology , Animals , COVID-19/drug therapy , Humans , Melatonin/therapeutic use , Reproducibility of Results , Seasons
19.
Mol Cell Biochem ; 477(3): 711-726, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1616202

ABSTRACT

The novel coronavirus pandemic has emerged as one of the significant medical-health challenges of the current century. The World Health Organization has named this new virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first detection of SARS-CoV-2 in November 2019 in Wuhan, China, physicians, researchers, and others have made it their top priority to find drugs and cures that can effectively treat patients and reduce mortality rates. The symptoms of Coronavirus Disease 2019 (COVID-19) include fever, dry cough, body aches, and anosmia. Various therapeutic compounds have been investigated and applied to mitigate the symptoms in COVID-19 patients and cure the disease. Degenerative virus analyses of the infection incidence and COVID-19 have demonstrated that SARS-CoV-2 penetrates the pulmonary alveoli's endothelial cells through Angiotensin-Converting Enzyme 2 (ACE2) receptors on the membrane, stimulates various signaling pathways and causes excessive secretion of cytokines. The continuous triggering of the innate and acquired immune system, as well as the overproduction of pro-inflammatory factors, cause a severe condition in the COVID-19 patients, which is called "cytokine storm". It can lead to acute respiratory distress syndrome (ARDS) in critical patients. Severe and critical COVID-19 cases demand oxygen therapy and mechanical ventilator support. Various drugs, including immunomodulatory and immunosuppressive agents (e.g., monoclonal antibodies (mAbs) and interleukin antagonists) have been utilized in clinical trials. However, the studies and clinical trials have documented diverging findings, which seem to be due to the differences in these drugs' possible mechanisms of action. These drugs' mechanism of action generally includes suppressing or modulating the immune system, preventing the development of cytokine storm via various signaling pathways, and enhancing the blood vessels' diameter in the lungs. In this review article, multiple medications from different drug families are discussed, and their possible mechanisms of action are also described.


Subject(s)
Antiviral Agents/immunology , COVID-19/drug therapy , Immunomodulating Agents/pharmacology , Antibodies, Monoclonal, Humanized/immunology , Antibodies, Monoclonal, Humanized/pharmacology , Antiviral Agents/pharmacology , Azetidines/immunology , Azetidines/pharmacology , COVID-19/etiology , Dexamethasone/immunology , Dexamethasone/pharmacology , Famotidine/immunology , Famotidine/pharmacology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/immunology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Infliximab/immunology , Infliximab/pharmacology , Interleukin 1 Receptor Antagonist Protein/immunology , Interleukin 1 Receptor Antagonist Protein/pharmacology , Melatonin/immunology , Melatonin/pharmacology , Purines/immunology , Purines/pharmacology , Pyrazoles/immunology , Pyrazoles/pharmacology , Sulfonamides/immunology , Sulfonamides/pharmacology
20.
J Pineal Res ; 72(2): e12782, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1597864

ABSTRACT

Melatonin is commonly used for sleep and jetlag at low doses. However, there is less documentation on the safety of higher doses, which are being increasingly used for a wide variety of conditions, including more recently COVID-19 prevention and treatment. The aim of this review was to investigate the safety of higher doses of melatonin in adults. Medline, Scopus, Embase and PsycINFO databases from inception until December 2019 with convenience searches until October 2020. Randomised controlled trials investigating high-dose melatonin (≥10 mg) in human adults over 30 years of age were included. Two investigators independently abstracted articles using PRISMA guidelines. Risk of bias was assessed by a committee of three investigators. 79 studies were identified with a total of 3861 participants. Studies included a large range of medical conditions. The meta-analysis was pooled data using a random effects model. The outcomes examined were the number of adverse events (AEs), serious adverse events (SAEs) and withdrawals due to AEs. A total of 29 studies (37%) made no mention of the presence or absence of AEs. Overall, only four studies met the pre-specified low risk of bias criteria for meta-analysis. In that small subset, melatonin did not cause a detectable increase in SAEs (Rate Ratio = 0.88 [0.52, 1.50], p = .64) or withdrawals due to AEs (0.93 [0.24, 3.56], p = .92), but did appear to increase the risk of AEs such as drowsiness, headache and dizziness (1.40 [1.15, 1.69], p < .001). Overall, there has been limited AE reporting from high-dose melatonin studies. Based on this limited evidence, melatonin appears to have a good safety profile. Better safety reporting in future long-term trials is needed to confirm this as our confidence limits were very wide due to the paucity of suitable data.


Subject(s)
COVID-19 , Melatonin , Adult , Humans , Melatonin/pharmacology , SARS-CoV-2 , Sleep
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