A mid-pandemic night's dream: Melatonin, from harbinger of anti-inflammation to mitochondrial savior in acute and long COVID-19 (Review)

Coronavirus disease 2019 (COVID-19), a systemic illness caused by severe acute respiratory distress syndrome 2 (SARS-CoV-2), has triggered a worldwide pandemic with symptoms ranging from asymptomatic to chronic, affecting practically every organ. Melatonin, an ancient antioxidant found in all living organisms, has been suggested as a safe and effective therapeutic option for the treatment of SARS-CoV-2 infection due to its good safety characteristics and broad-spectrum antiviral medication properties. Melatonin is essential in various metabolic pathways and governs physiological processes, such as the sleep-wake cycle and circadian rhythms. It exhibits oncostatic, anti-inflammatory, antioxidant and anti-aging properties, exhibiting promise for use in the treatment of numerous disorders, including COVID-19. The preventive and therapeutic effects of melatonin have been widely explored in a number of conditions and have been well-established in experimental ischemia/reperfusion investigations, particularly in coronary heart disease and stroke. Clinical research evaluating the use of melatonin in COVID-19 has shown various improved outcomes, including reduced hospitalization durations; however, the trials are small. Melatonin can alleviate mitochondrial dysfunction in COVID-19, improve immune cell function and provide antioxidant properties. However, its therapeutic potential remains underexplored due to funding limitations and thus further investigations are required.