Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality

[1]  M. Schwaninger,et al.  Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels , 2022, Cellular and Molecular Life Sciences.

[2]  M. Rayment,et al.  Caution required with use of ritonavir-boosted PF-07321332 in COVID-19 management , 2021, The Lancet.

[3]  R. Tiwari,et al.  Omicron (B.1.1.529 variant of SARS‐CoV‐2); an emerging threat: Current global scenario , 2021, Journal of medical virology.

[4]  K. Stebelová,et al.  Interactions of renin-angiotensin system and COVID-19: the importance of daily rhythms in ACE2, ADAM17 and TMPRSS2 expression. , 2021, Physiological research.

[5]  J. Tanaka,et al.  Sequential dynamics of virological and serological changes in the serum of SARS‐CoV‐2 infected patients , 2021, Journal of medical virology.

[6]  C. Bologna,et al.  Efficacy of Prolonged-Release Melatonin 2 mg (PRM 2 mg) Prescribed for Insomnia in Hospitalized Patients for COVID-19: A Retrospective Observational Study , 2021, Journal of clinical medicine.

[7]  T. Nyman,et al.  Inflammasomes and SARS-CoV-2 Infection , 2021, Viruses.

[8]  S. Bhatia,et al.  CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target , 2021, Science of The Total Environment.

[9]  Dongdong Wu,et al.  The Complex Interplay between Autophagy and NLRP3 Inflammasome in Renal Diseases , 2021, International journal of molecular sciences.

[10]  Michael McCoy.  Pfizer to license COVID-19 antiviral , 2021, Chemical & Engineering News.

[11]  B. Venkatraja,et al.  The Dominance of Severe Acute Respiratory Syndrome Coronavirus 2 B.1.617 and Its Sublineages and Associations with Mortality during the COVID-19 Pandemic in India between 2020 and 2021 , 2021, The American journal of tropical medicine and hygiene.

[12]  Elisabeth Mahase.  Covid-19: UK becomes first country to authorise antiviral molnupiravir , 2021, BMJ.

[13]  Rui Feng,et al.  The ameliorative effect of melatonin on LPS-induced Sertoli cells inflammatory and tight junctions damage via suppression of the TLR4/MyD88/NF-κB signaling pathway in newborn calf. , 2021, Theriogenology.

[14]  R. Singh,et al.  Role of toll‐like receptors in modulation of cytokine storm signaling in SARS‐CoV‐2‐induced COVID‐19 , 2021, Journal of medical virology.

[15]  Caizheng Yu,et al.  Kinetics of Neutralizing Antibody Response Underscores Clinical COVID-19 Progression , 2021, Journal of immunology research.

[16]  Z. T. Hasan,et al.  The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients , 2021, International Journal of Infectious Diseases.

[17]  E. Cecon,et al.  Therapeutic potential of melatonin and melatonergic drugs on K18‐hACE2 mice infected with SARS‐CoV‐2 , 2021, Journal of pineal research.

[18]  K. Dhama,et al.  Bats and viruses: a death-defying friendship , 2021, VirusDisease.

[19]  R. Alizadeh-Navaei,et al.  Melatonin effects on sleep quality and outcomes of COVID‐19 patients: An open‐label, randomized, controlled trial , 2021, Journal of medical virology.

[20]  T. Kawai,et al.  Meta-analysis of single-cell RNA-seq data reveals phenotypic switching of immune cells in severe COVID-19 patients , 2021, Computers in Biology and Medicine.

[21]  Z. Pourpak,et al.  A Pilot Study on Controlling Coronavirus Disease 2019 (COVID-19) Inflammation Using Melatonin Supplement. , 2021, Iranian journal of allergy, asthma, and immunology.

[22]  M. Sánchez-González,et al.  What if melatonin could help COVID-19 severe patients? , 2021, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[23]  M. Ratajczak,et al.  An evidence that SARS-Cov-2/COVID-19 spike protein (SP) damages hematopoietic stem/progenitor cells in the mechanism of pyroptosis in Nlrp3 inflammasome-dependent manner , 2021, Leukemia.

[24]  J Zhang,et al.  Melatonin and other indoles show antiviral activities against swine coronaviruses in vitro at pharmacological concentrations , 2021, Journal of pineal research.

[25]  Y. Liu,et al.  Protective effects of melatonin on the white matter damage of neonatal rats by regulating NLRP3 inflammasome activity , 2021, Neuroreport.

[26]  D. Skene,et al.  Exogenous melatonin decreases circadian misalignment and body weight among early types , 2021, Journal of pineal research.

[27]  B. Albensi,et al.  The Effect of COVID-19 on NF-κB and Neurological Manifestations of Disease , 2021, Molecular Neurobiology.

[28]  Gholamreza Farnoosh,et al.  Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment , 2021, European Journal of Pharmacology.

[29]  Fan Zhang,et al.  Glycemic Profile of Intravenous Dexamethasone-Induced Hyperglycemia Using Continuous Glucose Monitoring , 2021, The American journal of case reports.

[30]  P. Yenchitsomanus,et al.  Melatonin Inhibits Dengue Virus Infection via the Sirtuin 1-Mediated Interferon Pathway , 2021, Viruses.

[31]  Q. Cai,et al.  Exogenous melatonin alleviates hemorrhagic shock-induced hepatic ischemic injury in rats by inhibiting the NF-κB/IκBα signaling pathway , 2021, Molecular medicine reports.

[32]  R. Mohammadinejad,et al.  Anti-Inflammatory Activity of Melatonin: a Focus on the Role of NLRP3 Inflammasome , 2021, Inflammation.

[33]  A. Sen.  Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19? , 2021, Medical Hypotheses.

[34]  A. Sen.  Does serotonin deficiency lead to anosmia, ageusia and dysfunctional chemesthesis in COVID-19? , 2021 .

[35]  S. Jin,et al.  Systemic corticosteroids for management of COVID-19: Saving lives or causing harm? , 2021, International journal of immunopathology and pharmacology.

[36]  Zhaohui Zheng,et al.  CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells , 2020, Signal Transduction and Targeted Therapy.

[37]  F. Cheng,et al.  A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19 , 2020, PLoS biology.

[38]  G. Sygitowicz,et al.  Molecular mechanisms of organ damage in sepsis: an overview , 2020, The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases.

[39]  N. Tatonetti,et al.  Melatonin is significantly associated with survival of intubated COVID-19 patients , 2020, medRxiv.

[40]  J. Tesarik.  Melatonin attenuates growth factor receptor signaling required for SARS-CoV-2 replication , 2020 .

[41]  D. Zipeto,et al.  ACE2/ADAM17/TMPRSS2 Interplay May Be the Main Risk Factor for COVID-19 , 2020, Frontiers in Immunology.

[42]  D. Cardinali,et al.  Elderly as a High-risk Group during COVID-19 Pandemic: Effect of Circadian Misalignment, Sleep Dysregulation and Melatonin Administration , 2020, Sleep and Vigilance.

[43]  R. Hardeland,et al.  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, Molecules.

[44]  D. Ho,et al.  Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2 , 2020, Research square.

[45]  P. Oliver,et al.  ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease , 2020, Antioxidants.

[46]  G. B. L. de Freitas,et al.  COVID-19: Rational discovery of the therapeutic potential of Melatonin as a SARS-CoV-2 main Protease Inhibitor , 2020, International journal of medical sciences.

[47]  B. Tiwary,et al.  Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis , 2020, Life Sciences.

[48]  N. Schmidt,et al.  Overview: Systemic Inflammatory Response Derived From Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19 , 2020, Frontiers in Immunology.

[49]  D. Loh.  The potential of melatonin in the prevention and attenuation of oxidative hemolysis and myocardial injury from cd147 SARS-CoV-2 spike protein receptor binding , 2020 .

[50]  R. Reiter,et al.  Plasticity of glucose metabolism in activated immune cells: advantages for melatonin inhibition of COVID-19 disease , 2020 .

[51]  R. Reiter,et al.  Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series , 2020 .

[52]  R. Hardeland,et al.  Estimated doses of melatonin for treating deadly virus infections: focus on COVID-19 , 2020 .

[53]  R. Reiter,et al.  Is melatonin deficiency a unifying pathomechanism of high risk patients with COVID-19? , 2020, Life Sciences.

[54]  J. González‐Gallego,et al.  Melatonin modulates mitophagy, innate immunity and circadian clocks in a model of viral‐induced fulminant hepatic failure , 2020, Journal of cellular and molecular medicine.

[55]  P. Marik,et al.  Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19 , 2020, Frontiers in Medicine.

[56]  S. Ciesek,et al.  Growth Factor Receptor Signaling Inhibition Prevents SARS-CoV-2 Replication , 2020, bioRxiv.

[57]  A. Mirzazadeh,et al.  Epidemiological characteristics of COVID-19: a systematic review and meta-analysis , 2020, Epidemiology and Infection.

[58]  D. Tan,et al.  Potential utility of melatonin in deadly infectious diseases related to the overreaction of innate immune response and destructive inflammation: focus on COVID-19 , 2020 .

[59]  R. Reiter,et al.  COVID-19: Melatonin as a potential adjuvant treatment , 2020, Life Sciences.

[60]  Xiaomin Wang,et al.  Melatonin inhibits cytosolic mitochondrial-DNA induced neuroinflammatory signaling in accelerated aging and neurodegeneration. , 2020, The Journal of clinical investigation.

[61]  F. Cheng,et al.  Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2 , 2020, Cell Discovery.

[62]  E. Sahna,et al.  Ischemic postconditioning reduced myocardial ischemia-reperfusion injury: The roles of melatonin and uncoupling protein 3 , 2019, Anatolian journal of cardiology.

[63]  Fuxue Chen,et al.  Melatonin decreases M1 polarization via attenuating mitochondrial oxidative damage depending on UCP2 pathway in prorenin-treated microglia , 2019, PloS one.

[64]  J. Casado,et al.  Melatonin enhances responsiveness to Dichelobacter nodosus vaccine in sheep and increases peripheral blood CD4 T lymphocytes and IgG-expressing B lymphocytes. , 2018, Veterinary immunology and immunopathology.

[65]  Jian-Hua Luo,et al.  Melatonin mediated Foxp3‐downregulation decreases cytokines production via the TLR2 and TLR4 pathways in H. pylori infected mice , 2018, International immunopharmacology.

[66]  Jing Zhang,et al.  Melatonin suppresses TLR9-triggered proinflammatory cytokine production in macrophages by inhibiting ERK1/2 and AKT activation , 2018, Scientific Reports.

[67]  Yunhe Fu,et al.  Melatonin inhibits endoplasmic reticulum stress‐associated TXNIP/NLRP3 inflammasome activation in lipopolysaccharide‐induced endometritis in mice , 2018, International immunopharmacology.

[68]  T. Kepler,et al.  The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity , 2018, Cell.

[69]  L. Su,et al.  Melatonin Balance the Autophagy and Apoptosis by Regulating UCP2 in the LPS-Induced Cardiomyopathy , 2018, Molecules.

[70]  R. Reiter,et al.  Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions , 2018, Molecules.

[71]  R. Reiter,et al.  Clinical Uses of Melatonin in Neurological Diseases and Mental and Behavioural Disorders. , 2017, Current medicinal chemistry.

[72]  M. Pawłowska,et al.  Melatonin Supplementation Lowers Oxidative Stress and Regulates Adipokines in Obese Patients on a Calorie-Restricted Diet , 2017, Oxidative medicine and cellular longevity.

[73]  Guangyu Ying,et al.  Melatonin-mediated mitophagy protects against early brain injury after subarachnoid hemorrhage through inhibition of NLRP3 inflammasome activation , 2017, Scientific Reports.

[74]  C. Zhang,et al.  Melatonin attenuates angiotensin II-induced abdominal aortic aneurysm through the down-regulation of matrix metalloproteinases , 2017, Oncotarget.

[75]  C. González-Yanes,et al.  Possible Involvement of the Inhibition of NF‐κB Factor in Anti‐Inflammatory Actions That Melatonin Exerts on Mast Cells , 2016, Journal of cellular biochemistry.

[76]  G. Gao,et al.  Melatonin alleviates acute lung injury through inhibiting the NLRP3 inflammasome , 2016, Journal of pineal research.

[77]  Da‐long Ren,et al.  Exogenous melatonin inhibits neutrophil migration through suppression of ERK activation. , 2015, The Journal of endocrinology.

[78]  Huaxi Xu,et al.  Melatonin stimulates the nonamyloidogenic processing of βAPP through the positive transcriptional regulation of ADAM10 and ADAM17 , 2015, Journal of pineal research.

[79]  S. Perlman,et al.  Coronaviruses: An Overview of Their Replication and Pathogenesis , 2015, Methods in molecular biology.

[80]  R. Reiter,et al.  Fundamental Issues Related to the Origin of Melatonin and Melatonin Isomers during Evolution: Relation to Their Biological Functions , 2014, International journal of molecular sciences.

[81]  R. Reiter,et al.  Melatonin identified in meats and other food stuffs: potentially nutritional impact , 2014, Journal of pineal research.

[82]  E. Cecon,et al.  NF-κB Drives the Synthesis of Melatonin in RAW 264.7 Macrophages by Inducing the Transcription of the Arylalkylamine-N-Acetyltransferase (AA-NAT) Gene , 2012, PloS one.

[83]  R. Reiter,et al.  Beneficial actions of melatonin in the management of viral infections: a new use for this “molecular handyman”? , 2012, Reviews in medical virology.

[84]  L. Fuentes-Broto,et al.  Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity , 2011, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[85]  J. Calvo,et al.  Evidence of melatonin synthesis and release by mast cells. Possible modulatory role on inflammation. , 2010, Pharmacological research.

[86]  Young Min Kim,et al.  SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii , 2010, Bioorganic & Medicinal Chemistry Letters.

[87]  R. Hardeland.  Neuroprotection by Radical Avoidance: Search for Suitable Agents , 2009, Molecules.

[88]  J. Meseguer,et al.  In vivo actions of melatonin on the innate immune parameters in the teleost fish gilthead seabream , 2008, Journal of pineal research.

[89]  R. Reiter,et al.  One molecule, many derivatives: A never‐ending interaction of melatonin with reactive oxygen and nitrogen species? , 2007, Journal of pineal research.

[90]  R. Reiter,et al.  Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages , 2005, Journal of Neuroimmunology.

[91]  Xiaochao Ma,et al.  METABOLISM OF MELATONIN BY HUMAN CYTOCHROMES P450 , 2005, Drug Metabolism and Disposition.

[92]  Rolf Hilgenfeld,et al.  Coronavirus Main Proteinase (3CLpro) Structure: Basis for Design of Anti-SARS Drugs , 2003, Science.

[93]  R. Reiter,et al.  Mechanistic and comparative studies of melatonin and classic antioxidants in terms of their interactions with the ABTS cation radical , 2003, Journal of pineal research.

[94]  F. Herrera,et al.  Melatonin regulation of antioxidant enzyme gene expression , 2002, Cellular and Molecular Life Sciences CMLS.

[95]  S. Cuzzocrea,et al.  Melatonin reduces oxidative damage and increases survival of mice infected with Schistosoma mansoni. , 2002, Free radical biology & medicine.

[96]  D. Cardinali,et al.  Effect of Melatonin Treatment on 24‐h Variations in Responses to Mitogens and Lymphocyte Subset Populations in Rat Submaxillary Lymph Nodes , 2000, Journal of neuroendocrinology.

[97]  A Büki,et al.  Cytochrome c Release and Caspase Activation in Traumatic Axonal Injury , 2000, The Journal of Neuroscience.

[98]  E. Mazzon,et al.  Protective effects of melatonin in zymosan-activated plasma-induced paw inflammation. , 1998, European journal of pharmacology.

[99]  S. Cuzzocrea,et al.  Protective effect of melatonin in a non‐septic shock model induced by zymosan in the rat , 1998, Journal of pineal research.

[100]  S. Cuzzocrea,et al.  Protective effect of melatonin in carrageenan‐induced models of local inflammation: Relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity , 1997, Journal of pineal research.

[101]  J. Arendt,et al.  THE EFFECTS OF EXOGENOUS MELATONIN ON ENDOCRINE FUNCTION IN MAN , 1986, Clinical endocrinology.

[102]  R. Reiter,et al.  Melatonin: A potential therapeutic agent against COVID-19 , 2021 .

[103]  D. Cardinali,et al.  An urgent proposal for the immediate use of melatonin as an adjuvant to anti- SARS-CoV-2 vaccination , 2021 .

[104]  W. Lim,et al.  Dexamethasone in Hospitalized Patients with Covid-19 , 2021 .