Therapeutic Benefits of Melatonin against COVID-19

Abstract

The assumption of the pineal hormone melatonin as a therapeutic use for COVID-19-affected people seems promising. Its intake has shown significant improvement in the patients' conditions. Higher melatonin titers in children may provide a protective shield against this disease. The hormone melatonin works as an anti-inflammatory, antioxidant, immunomodulator, and strategically slows down the cytokine release which is observed in the COVID-19 disease, thereby improving the overall health of afflicted patients. The medical community is expected shortly to use remedial attributes like anti-inflammatory, antioxidant, antivirals, etc., of melatonin in the successful prevention and cure of COVID-19 morbidity. Thus, the administration of melatonin seems auspicious in the cure and prevention of this COVID-19 fatality. Moreover, melatonin does not seem to reduce the efficiency of approved vaccines against the SARS-CoV-2 virus. Melatonin increases the production of inflammatory cytokines and Th1 and enhances both humoral and cell-mediated responses. Through the enhanced humoral immunity, melatonin exhibits antiviral activities by suppressing multiple inflammatory products such as IL-6, IL1β, and tumor necrosis factor α, which are immediately released during lung injury of severe COVID-19. Hence, the novel use of melatonin along with other antivirals as an early treatment option against COVID-19 infection is suggested. Here, we have chalked out the invasion mechanisms and appropriate implications of the latest findings concerned with melatonin against the virus SARS-CoV-2. Nevertheless, within the setting of a clinical intervention, the promising compounds must go through a series of studies before their recommendation. In the clinical field, this is done in a time-ordered sequence, in line with the phase label affixed to proper protocol of trials: phase I-phase II and the final phase III. Nevertheless, while medical recommendations can only be made on the basis of reassuring evidence, there are still three issues worth considering before implementation: representativeness, validity, and lastly generalizability.

Keywords: COVID-19; Comorbidities; Cytokine; Melatonin; SARS-CoV-2; Therapeutic.

Fig. 1.

An outline of the SARS-CoV-2 virus life cycle (Source: Parasher [20]).

Fig. 2.

COVID-19 pathology – cytokine storm leading to death could effectively be reduced by the administration of melatonin (Source: Vlachou et al. [88]). The figure shows the probable mechanistic routes, where melatonin could deplete the infection process. Severe oxidation, inflammation, and a hyperactive immune response contribute to COVID-19 pathology, leading to a cytokine surge that causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and frequent deaths, which can be significantly lowered by the administration of melatonin.

Fig. 3.

Adjuvant therapeutic action of melatonin during COVID-19 infection (Source: Reiter et al. [76]). Melatonin was found to curtail the toxicity of hydroxychloroquine and increase its potency. This can be an exploratory protocol, a preliminary phase I/II study.

Fig. 4.

Humoral immunity and melatonin – a therapeutic approach with toremifene (Source: Cheng et al. [89]) – melatonin is evolutionarily conserved from bacteria to humans. Melatonin suppresses inflammatory pathways that include IL-6, IL1β, and TNFα, which are released during lung injury of severe COVID-19 infection. Toremifene which is a selective estrogen receptor modulator and FDA-approved to treat advanced breast cancer has shown several antiviral activities such as against the Ebola virus, MRES-CoV, SARS-CoV-1, and SARS-CoV-2. Hence, the synergistic antiviral and anti-inflammatory effects of melatonin and toremifene offer a promising treatment approach for COVID-19.