Melatonin interferes with COVID-19 at several distinct ROS-related steps

Abstract

Recent studies have shown a correlation between COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the distinct, exaggerated immune response titled “cytokine storm”. This immune response leads to excessive production and accumulation of reactive oxygen species (ROS) that cause clinical signs characteristic of COVID-19 such as decreased oxygen saturation, alteration of hemoglobin properties, decreased nitric oxide (NO) bioavailability, vasoconstriction, elevated cytokines, cardiac and/or renal injury, enhanced D-dimer, leukocytosis, and an increased neutrophil to lymphocyte ratio. Particularly, neutrophil myeloperoxidase (MPO) is thought to be especially abundant and, as a result, contributes substantially to oxidative stress and the pathophysiology of COVID-19. Conversely, melatonin, a potent MPO inhibitor, has been noted for its anti-inflammatory, anti-oxidative, anti-apoptotic, and neuroprotective actions. Melatonin has been proposed as a safe therapeutic agent for COVID-19 recently, having been given with a US Food and Drug Administration emergency authorized cocktail, REGEN-COV2, for management of COVID-19 progression. This review distinctly highlights both how the destructive interactions of HOCl with tetrapyrrole rings may contribute to oxygen deficiency and hypoxia, vitamin B12 deficiency, NO deficiency, increased oxidative stress, and sleep disturbance, as well as how melatonin acts to prevent these events, thereby improving COVID-19 prognosis.

Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection

“…Since the classification of SARS-CoV-2 infection as a pandemic, in excess of 140 publications have urged consideration of melatonin as a safe and potentially effective treatment for this worldwide disease [1][2][3][4][5][6][7][8][9][10][11][12][13]. The rationale for its use not only stems from its high safety profile [14][15][16] but also from its multiple beneficial actions in experimental and clinical studies related to the pandemic.…”

Melatonin and Related Compounds: Antioxidant and Anti-Inflammatory Actions

“…During the current pandemic, melatonin has been widely reported as being a potential therapeutic option against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) referred to as COVID-19 [23][24][25]. The rationale for using melatonin against this condition stems from the elevated oxidative activity and production of ROS and RNS observed in patients with COVID-19 [26,27].…”

COVID-19 at a Glance: An Up-to-Date Overview on Variants, Drug Design and Therapies

“…Recently, melatonin, the so-called ’hormone of darkness’, due to its synthesis at night-time, has attracted the interest of infectious diseases specialists and epidemiologists for its adjuvant role in treating patients with COVID-19 [ 118 ]. It has been recently given as part of a US Food and Drug Administration emergency authorized cocktail, REGEN-COV2, for the management of COVID-19 progression [ 119 ].…”