Review Article
Volume 13 Issue 4 - 2021
The Potential Applicability of Melatonin as an Immunosuppressive Agent for COVID-19: Reviews
Leila A Pallante1,2, Dhir N Gala1,2*, Abdullah Egiz2, Sarvin Farajzadeh-Asl2 and Gautam Ullal3
1American University of the Caribbean School of Medicine, Sint Maarten
2School of Medicine, University of Central Lancashire, Preston, UK
3Professor of Neuroscience, American University of the Caribbean School of Medicine, Sint Maarten
*Corresponding Author: Dhir N Gala, American University of the Caribbean School of Medicine, Sint Maarten.
Received: February 16, 2021; Published: March 15, 2021


COVID-19 is an emerging pathogen that has recently caused a global pandemic. It is an RNA virus that causes a respiratory tract infection. The pathogenesis of this virus involves an over aggressive immune reaction leading to inflammation and in certain cases acute respiratory distress syndrome (ARDS) and various neurological manifestations. Melatonin, a mitochondrially targeted antioxidant with anti-inflammatory properties, is being tested in trials as a potential adjuvant therapeutic agent that can help reduce oxidative stress damage caused by viral infections as well as optimizing the innate immune response. In addition, melatonin is an extremely safe drug and reports show its usefulness in treating other respiratory viral infections. The role of melatonin as an adjuvant in managing COVID-19 cases as well as the delirious states that are often encountered in these patients is being discussed.

Keywords: COVID-19; SARS-CoV-2; Melatonin; immunomodulation; Oxidative Stress; Prevention; Immunosuppression; Prophylaxis


  1. Wang X and Ding YQ. “From SARS to COVID-19: Pathogens, receptor, pathogenesis and principles of the treatment”. Zhonghua Bing Li Xue Za Zhi 6 (2020): 647-652.
  2. Weiss SR and Navas-Martin S. “Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus”. Microbiology and Molecular Biology Reviews 4 (2005): 635.
  3. Guo Y., et al. “The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status”. Military Medical Research 1 (2020): 11.
  4. Rothan HA and Byrareddy SN. “The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak”. Journal of Autoimmunity 109 (2020): 102433.
  5. Mirfazeli FS., et al. “Neuropsychiatric manifestations of COVID-19 can be clustered in three distinct symptom categories”. Scientific Reports 1 (2020): 20957.
  6. Sharifian-Dorche M., et al. “Neurological complications of coronavirus infection; a comparative review and lessons learned during the COVID-19 pandemic”. Journal of the Neurological Sciences 417 (2020): 117085.
  7. Scheidl E., et al. “Guillain-barre syndrome during SARS-CoV-2 pandemic: A case report and review of recent literature”. The Journal of the Peripheral Nervous System 2 (2020): 204-207.
  8. World Health Organisation. WHO Coronavirus (COVID-19) Dashboard (2021).
  9. Bosch BJ., et al. “The coronavirus spike protein is a class I virus fusion protein: Structural and functional characterization of the fusion core complex”. Journal of Virology 16 (2003): 8801-8811.
  10. Li W., et al. “Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus”. Nature6965 (2003): 450-454.
  11. Zou X., et al. “Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection”. Frontiers in Medicine 2 (2020): 185-192.
  12. Kim YM., et al. “Neutrophil elastase is produced by pulmonary artery smooth muscle cells and is linked to neointimal lesions”. The American Journal of Pathology 3 (2011): 1560-1572.
  13. Boopathi S., et al. “Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment”. Journal of Biomolecular Structure and Dynamics (2020): 1-10.
  14. Felsenstein S., et al. “COVID-19: Immunology and treatment options”. Clinical Immunology 215 (2020): 108448.
  15. Imami AS., et al. “Oxytocin's anti-inflammatory and proimmune functions in COVID-19: A transcriptomic signature-based approach”. The Physiological Genomics 52.9 (2020): 401-407.
  16. Banerjee D and Viswanath B. “Neuropsychiatric manifestations of COVID-19 and possible pathogenic mechanisms: Insights from other coronaviruses”. Asian Journal of Psychiatry 54 (2020): 102350.
  17. Coolen T., et al. “Early postmortem brain MRI findings in COVID-19 non-survivors”. Neurology14 (2020): e2016.
  18. Brann DH., et al. “Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia”. Science Advances 31 (2020): eabc5801.
  19. Bostancıklıoğlu M. “Temporal correlation between neurological and gastrointestinal symptoms of SARS-CoV-2”. Inflammatory Bowel Diseases 8 (2020): e89-91.
  20. Qin W., et al. “Melatonin protects blood-brain barrier integrity and permeability by inhibiting matrix metalloproteinase-9 via the NOTCH3/NF-kappaB pathway”. Aging (Albany NY) 23 (2019): 11391-11415.
  21. Tordjman S., et al. “Melatonin: Pharmacology, functions and therapeutic benefits”. Current Neuropharmacology 15.3 (2017): 434-443.
  22. Galano A., et al. “Melatonin as a natural ally against oxidative stress: A physicochemical examination”. Journal of Pineal Research 1 (2011): 1-16.
  23. Reiter RJ., et al. “Melatonin as a mitochondria-targeted antioxidant: One of evolution's best ideas”. Cellular and Molecular Life Sciences 21 (2017): 3863-3881.
  24. Shneider A., et al. “Can melatonin reduce the severity of COVID-19 pandemic?” International Reviews of Immunology 4 (2020): 153-162.
  25. Claustrat B., et al. “The basic physiology and pathophysiology of melatonin”. Sleep Medicine Review 1 (2005): 11-24.
  26. Lynch HJ., et al. “Daily rhythm in human urinary melatonin”. Science 4172 (1975): 169-171.
  27. Karami Z., et al. “Effect of daylight on melatonin and subjective general health factors in elderly people”. Iranian Journal of Public Health 5 (2016): 636-643.
  28. Cardinali DP., et al. “Can melatonin be a potential "silver bullet" in treating COVID-19 patients?” Diseases 4 (2020): 44.
  29. Karasek M and Winczyk K. “Melatonin in humans”. The Indian Journal of Physiology and Pharmacology 5 (2006): 19-39.
  30. Hardeland R. “Melatonin and inflammation-story of a double-edged blade”. Journal of Pineal Researc 4 (2018): e12525.
  31. Imai Y., et al. “Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury”. Cell 2 (2008): 235-249.
  32. Zhao Y., et al. “Melatonin attenuates white matter damage after focal brain ischemia in rats by regulating the TLR4/NF-kappaB pathway”. Brain Res Bull 150 (2019): 168-178.
  33. Alluri H., et al. “Melatonin preserves blood-brain barrier integrity and permeability via matrix metalloproteinase-9 inhibition”. PLoS One 5 (2016): e0154427.
  34. Hu Y., et al. “Melatonin protects against blood-brain barrier damage by inhibiting the TLR4/ NF-kappaB signaling pathway after LPS treatment in neonatal rats”. Oncotarget19 (2017): 31638-31654.
  35. Bahrampour Juybari K., et al. “Melatonin potentials against viral infections including COVID-19: Current evidence and new findings”. Virus Research 287 (2020): 198108.
  36. Huang SH., et al. “Melatonin decreases TLR3-mediated inflammatory factor expression via inhibition of NF-kappa B activation in respiratory syncytial virus-infected RAW264.7 macrophages”. Journal of Pineal Research 1 (2008): 93-100.
  37. Huang SH., et al. “Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice”. Journal of Pineal Research 2 (2010):109-116.
  38. Huang S., et al. “Melatonin possesses an anti-influenza potential through its immune modulatory effect”. Journal of Functional Foods 58 (2019): 189-198.
  39. Yuan S. “Drugs to cure avian influenza infection--multiple ways to prevent cell death”. Cell Death and Disease 4 (2013): e835.
  40. Tay MZ., et al. “The trinity of COVID-19: Immunity, inflammation and intervention”. Nature Reviews Immunology 6 (2020): 363-374.
  41. Shao H., et al. “Upregulation of mitochondrial gene expression in PBMC from convalescent SARS patients”. Journal of Clinical Immunology 6 (2006): 546-554.
  42. Srinivasan V., et al. “Melatonin, immune function and aging”. Immun Ageing 2 (2005): 17.
  43. Bondy SC., et al. “Retardation of brain aging by chronic treatment with melatonin”. Annals of the New York Academy of Sciences 1035 (2004): 197-215.
  44. Palmblad J., et al. “Stressor exposure and immunological response in man: Interferon-producing capacity and phagocytosis”. Journal of Psychosomatic Research 3 (1976): 193-199.
  45. Acuna-Castroviejo D., et al. “Clinical trial to test the efficacy of melatonin in COVID-19”. Journal of Pineal Research 3 (2020): e12683.
  46. El-Missiry MA., et al. “Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of covid-19”. European Journal of Pharmacology 882 (2020): 173329.
  47. Tan DX and Hardeland R. “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).
  48. Zambrelli E., et al. “Delirium and sleep disturbances in COVID-19: A possible role for melatonin in hospitalized patients?” Sleep Medicine 70 (2020): 111.
  49. Zhang Q., et al. “Prophylactic use of exogenous melatonin and melatonin receptor agonists to improve sleep and delirium in the intensive care units: A systematic review and meta-analysis of randomized controlled trials”. Sleep and Breathing4 (2019): 1059-1070.
  50. Garcia JA., et al. “Disruption of the NF-kappaB/NLRP3 connection by melatonin requires retinoid-related orphan receptor-alpha and blocks the septic response in mice”. The FASEB Journal 9 (2015): 3863-3875.
Citation: Dhir N Gala., et al. “The Potential Applicability of Melatonin as an Immunosuppressive Agent for COVID-19: Review”. EC Neurology 13.4 (2021): 11-21.

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