Melatonin — A Promising Candidate for Prevention and Treatment of COVID-19

Figure 1.  I-MASK+ (Prophylaxis & Early Outpatient Treatment Protocol for Covid-19)

In Figure 1, it shows the prophylaxis protocol proposed by FLCCC Alliance.^[1] And, the below items on the proposed list:

• Vitamin D3
• Vitamin C
• Quercetin
• Zinc
• Melatonin

are added as immune boosters for fighting Covid-19 virus.

In this article, we will discuss what melatonin is.

Melatonin — A promising treatment option for COVID-19

Melatonin, a hormone secreted by the pineal gland that regulates the sleep-wake cycle and is commonly used as an over-the-counter sleep aid.  It has wide-ranging effects as an antioxidant, anti-inflammatory, and immunomodulatory compound.

Based on multiple studies, melatonin is believed to be a promising candidate for prevention and treatment of Covid-19:

• University of Toronto^[2]
• Based on scientists' review, they discuss evidence implying that melatonin
• Prevents SARS-of CoV-2 infection
• Is suitable as an effective anti-inflammatory/immunoregulatory/antioxidant agent
• Counteracts chronodisruption
• Combats several comorbidities such as diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases, which aggravate COVID-19 disease
• Exerts a neuroprotective effect in acutely and chronically affected SARS-CoV-2 patients
• Can be an adjuvant to potentiate anti-SARS-CoV-2 vaccines. 
• Lerner Research Institute^[3]
• According to the findings published on 11/06/2020, a novel artificial intelligence platform developed by Lerner Research Institute researchers to identify possible drugs for COVID-19 repurposing has revealed melatonin as a promising candidate.
• Cleveland Clinic^[4]
• Analysis of patient data from Cleveland Clinic’s COVID-19 registry revealed that melatonin usage was associated with a nearly 30% reduced likelihood of testing positive for SARS-CoV-2 after adjusting for age, race, smoking history and various disease comorbidities. 
• Notably, the reduced likelihood of testing positive for the virus increased from 30 to 52 percent for African Americans when adjusted for the same variables.

Conclusion

CD147 is a glycoprotein that is responsible for the cytokine storm in the lungs through the mediation of viral invasion. Melatonin use previously was shown to reduce cardiac damage by blocking the CD147 activity. Hence, melatonin, a safe drug, may prevent severe symptoms, reduce symptom severity and the adverse effects of the other antiviral drugs in COVID-19 patients. 

In [11], the authors concluded that the use of melatonin, which is reduced in the elderly and immune-compromised patients, should be considered as an adjuvant through its CD147 suppressor and immunomodulatory effect.  

PAK1 is considered as a pathogenic enzyme and its unusual activation could be responsible for a broad range of pathologic conditions such as aging, inflammation, malaria, cancers immunopathology, viral infections, etc.^[8]  

Interestingly, melatonin exerts a spectrum of important anti-PAK1 properties in some abnormal conditions such as sleep disturbance, immune system effectiveness reduction, infectious disorders, inflammation, cancer, painful conditions, etc.^[6]Although it is not scientifically confirmed as yet, PAK1-inhibitors (incl. melatonin) could theoretically exert as potential agents for the management of a recent outbreak of COVID-19 infection. 

Indeed, Russel Reiter, a pioneer in melatonin research, has recently emphasized that melatonin may be incorporated into the treatment of COVID-19 as an alternative or adjuvant.^[6]

References

1. FLCCC Alliance (Front Line Covid-19 Critical Care Alliance)
2. Cardinali, D., Brown, G., and Pandi-Peruman, S. (2020). Can Melatonin Be a Potential “Silver Bullet” in Treating COVID-19 Patients? Diseases.
3. A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19
4. Melatonin a Promising Candidate for Prevention and Treatment of COVID-19
5. Melatonin potentials against viral infections including COVID-19: Current evidence and new findings
6. Maruta H., He H. PAK1-blockers: potential therapeutics against COVID-19. Med. Drug Discov. 2020
7. Melatonin: Breakthrough Discoveries That Can Help You Combat Aging, Boost Your Immune System, Reduce Your Risk of Cancer and Heart Disease, Get a Better Night's Sleep Paperback – July 1, 1996
8. Maruta H. Herbal therapeutics that block the oncogenic kinase PAK1: a practical approach towards PAK1‐dependent diseases and longevity. Phytother. Res. 2014;28(5):656–672.
9. Melatonin potentials against viral infections including COVID-19: Current evidence and new findings
10. Öztürk G, Akbulut KG, Güney Ş. Turk J Med Sci. 2020 Oct 22; 50(6):1504-1512. Epub 2020 Oct 22.
11. Sehirli AO, Sayiner S, Serakinci N. Mol Biol Rep. 2020 Oct; 47(10):8229-8233. Epub 2020 Sep 12.