Sleep and No-Sickness? The Preventative Impact of Melatonin on Covid-19 Patients

 

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Being the hardworking students that we are, we tend to allow our sleep schedules to fall out of “circadian-rhythm” (haha get it?). We tend to give into the marketing of pretty Starbucks coffee drinks to keep us awake and the idea of studying for hours prioritizing good grades over getting a good night’s sleep. This contributes to the 50 to 70 million Americans who suffer from sleep disorders or sleep deprivation and more than 60 million Americans who take sleep medications every year. It is estimated that Americans spend more than $41 billion on sleep aids and remedies (Penn Medicine). But sleeping issues have been around since our earliest existence, so what did we do before?

 

When we think of sleep remedies, we can look back as early as early Egyptian and ancient Roman times. One of the most well-known ancient remedies is chamomile. Not only was it great for sleeping issues but has many other positive effects including its ability to act as a cold remedy (Wise Ape, 2021). Today we often use it as a common nighttime staple to help us sleep and relax. However, for some people it does not work, or they need something stronger to aid their sleep. This is where the understanding and pharmacological production of melatonin became a game changer to the sleep-deprived people of the world and now possibly Covid-19 patients? First, let’s understand where melatonin comes from.

 

Melatonin is a natural hormone that is produced by our pineal gland. It is a derivative of tryptophan, an important amino acid necessary for maintaining of many of bodily functions. It was first isolated by Aaron B Lerner in 1958 of Yale University School of Medicine when he was conducting vitiligo research on frogs. He isolated a hormone melatonin thinking it would lighten the skin of frogs, only it didn’t. Instead, he found that it was responsible for maintaining cycles of wakefulness and rest. With respect to its target, melatonin binds to two type of G-protein receptors, MT1 and MT2, in the suprachiasmatic nucleus, a tiny region of the hypothalamus in the brain. High levels of melatonin can induce sleep. When our sleep schedule is normal, darkness prompts our pineal gland to secrete melatonin. The lack of melatonin production during the day will elicit wakefulness. This is why if your sleep schedule is off because you are doing things like staring at your phone until 2am, you are exposing yourself to blue light which will not let you produce melatonin. Now you are a walking zombie at your 8am class because you got no sleep. However, as important as melatonin is to sleep, it has been found to have other amazing benefits, including helping in learning and memory, fertility and reproduction, and most-recently immune activity (Srinivasan et al., 2005). This finding has been used to explore its benefits to Covid-19 patients.

 

SARS-CoV-2 can cause severe inflammatory responses and oxidative stress; two biological events alleviated by melatonin. One way melatonin can act is by reducing oxidative stress through its ability to increase an antioxidant known as glutathione. Glutathione is an important antioxidant that combats damage within cells, such as free radicals. With respect to COVID-19, a common symptom resulting from viral infection is oxidative stress caused by an increase in free radicals. Thus, melatonin can increase glutathione levels and reduce conditions of oxidative stress in COVID-19 patients. In addition, melatonin has anti-inflammatory abilities which arise from its affinity to G-protein-coupled receptors which control the secondary signaling pathways that impact the immune response. With respect to COVID-19, the infecting SARS-CoV-2 virus binds with high affinity to angiotensin-converting enzyme 2 (ACE2) receptors on the epithelial lining of the lungs. This binding triggers a proinflammatory response. However, calmodulin, an important messenger protein in the G-protein-coupled secondary pathway, controls the amount of ACE2 receptors on the plasma membrane. Melatonin can inhibit the coupling of ACE2 receptors and SAR-COV2 during viral particle fusion through its inhibition of calmodulin as it is regulated by the secondary messenger pathway (Cross et al., 2021). But if you don’t believe me, just look at how complex melatonin’s target pathway is (Cecon et al., 2017).

Fig. 1. Melatonin receptor pathway. Graph from E Cecon et al., Melatonin receptors: molecular pharmacology and signaling in the context of system bias. British Journal of Pharmacology. (5 July 2017).

Complex, I know! There are so many other ways melatonin has proven to be a great drug for other disease use other than just sleep. But from those short explanations on how melatonin can work, you get the idea. This is an incredible new form of exploration that can truly help so many people fighting COVID-19. As incredible as these findings do sound, we are still exploring the full accuracy and positive effectiveness of this drug on COVID-19 patients. More importantly, it is imperative to stay on top of new research and findings as we are constantly at risk of COVID-19 as the world begins opening up again. So now we ask the big question, do we bring this idea further to light that COVID-19 is a potential drug market for COVID-19? Researchers have already explored melatonin’s benefits in viral disease similar to COVID-19 so why not to treat COVID-19 patients? One problem is that we could be risking another “Ivermectin” fiasco, with multiple people storming our local CVS and buying all of the over-the counter melatonin thinking it can completely fight COVID-19 (only this being a much safer and beneficial option if you are a struggling college student who never sleeps). What do you think?

By Sarah Mandviwala, A Master's of Medical Science Student at the University of Kentucky

 

Works Cited

Ape, T. W. (2018, April 17). The history of chamomile tea. Wise Ape. Retrieved October 12, 2021, from https://www.wiseapetea.com/blogs/knowledge/the-history-of-chamomile-tea.

Cecon, E., Oishi, A., & Jockers, R. (2017, August 17). BPS Publications. British Pharmacological Society | Journals. Retrieved October 12, 2021, from https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.13950#:~:text=Melatonin%20receptor%20signalling%20pathways.,and%20increase%20in%20intracellular%20Ca2%2B.

Cross, K. M., Landis, D. M., Sehgal, L., & Payne, J. D. (2021, August). Melatonin for the early treatment of covid-19: A narrative review of current evidence and possible efficacy. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. Retrieved October 12, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190272/#bib38.

Melatonin and zolpidem: Do sleeping aids actually work? Penn Medicine. (n.d.). Retrieved October 12, 2021, from https://www.pennmedicine.org/updates/blogs/health-and-wellness/2018/july/sleeping-aids.

Srinivasan, V., Maestroni, G. J. M., Cardinali, D. P., Esquifino, A. I., Perumal, S. R. P., & Miller, S. C. (2005, November 29). Melatonin, Immune Function and aging. Immunity & ageing : I & A. Retrieved October 12, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1325257/.