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

• Published in: Journal of inorganic biochemistry 2021-10, Vol.223, p.111546-111546, Article 111546
• Main Authors: Camp, Olivia G., Bai, David, Gonullu, Damla C., Nayak, Neha, Abu-Soud, Husam M.
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents - pharmacology; Antioxidants - pharmacology; Apoptosis - drug effects; COVID-19; COVID-19 - immunology; COVID-19 - metabolism; COVID-19 Drug Treatment; Cytokine Release Syndrome - immunology; Cytokines - metabolism; Hemeproteins - metabolism; Hemoprotein; Humans; Hypochlorous Acid - metabolism; Inflammation; Mammalian peroxidase; Melatonin; Melatonin - pharmacology; Nitric Oxide - metabolism; Oxidation-Reduction; Oxidative Stress - drug effects; Peroxidase - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Review; SARS-CoV-2; Sleep; Sleep - drug effects; Vitamin B Deficiency - metabolism
• ISSN: 0162-0134; 1873-3344; 1873-3344
• DOI: 10.1016/j.jinorgbio.2021.111546

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. 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. [Display omitted] •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