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

https://doi.org/10.1016/j.jinorgbio.2021.111546Get rights and content

Highlights

  • SARS-CoV-2 infection generates overwhelming levels of neutrophil myeloperoxidase

  • Hypochlorous acid and other reactive oxygen species destroy tetrapyrrole rings

  • This causes nitric oxide, oxygen, and vitamin B12 deficiencies; markers of COVID-19

  • Melatonin inhibits myeloperoxidase activity and scavenges reactive oxygen species

  • Melatonin supplements can prevent pathophysiological consequences of COVID-19 disease

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.

Graphical abstract

The proposed pathway of SAR-CoV-2 infection associated with an uncontrolled immune response and cytokine storm generating MPO and ROS resulting in decreased NO and vasoconstriction, decreased O2 and hypoxia, and vitamin B12 deficiency through tetrapyrrole ring destruction, and the prevention by melatonin.

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Keywords

COVID-19
Melatonin
Mammalian peroxidase
Reactive oxygen species
Inflammation
Hemoprotein
Sleep

Abbreviations

MPO
myeloperoxidase
ROS
reactive oxygen species
O2•-
superoxide
H2O2
hydrogen peroxide
OH
hydroxyl radical
ONOO
and peroxynitrite
NETs
neutrophil extracellular traps
HOCl
hypochlorous acid
NOS
nitric oxide synthase
NO
nitric oxide
Hb
hemoglobin
iNOS
inducible nitric oxide synthase
Fe
iron
H4B
tetrahydrobiopterin
NOHA
N-hydroxyarginine
CAT
catalase
CNCl
cyanogen chloride
Co
cobalt
MMP
matrix metalloproteinase
HSA
human serum albumin

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1

These authors contributed equally to this manuscript.

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