In addition to anti-inflammation, anti-oxidation, biological rhythms resynchronization, and sleep induction, melatonin has multiple biological impacts, including apoptosis induction and immunomodulation (Carlberg, 2000; Pourhanifeh et al., 2020). Crucial effects of melatonin such as oncostatic properties are mediated through receptor-independent and receptor-dependent mechanisms (Srinivasan et al., 2008). Rossi, 2013). It is well-known that melatonin as an anti-oxidative and anti-inflammatory agent counters acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induced by viral and bacterial infections. Melatonin can be beneficial in critically ill patients reducing vessel permeability, inducing sedation, decreasing agitation and increasing sleep quality. These beneficial Androsterone properties of melatonin may highlight this hypothesis that melatonin may exert further clinical outcomes for COVID-19 patients (Zhang et al., 2020b). This review aimed to summarize available data on melatonin therapeutic effects on viral infections with focus on coronaviruses, especially coronavirus disease 2019 (COVID-19). 2.?Melatonin and its potentials As mentioned earlier, melatonin is primarily secreted from the pineal gland during the dark period of a circadian cycle (Dubocovich, 1988). Circadian rhythm disruption interferes with nocturnal melatonin signals leading to the impairment of several physiologic cell actions and homeostatic metabolic rhythms causing acceleration of malignancy (Stevens et al., 2014). Melatonin interacts with numerous cellular proteins such as signaling molecules, transporters, channels, and enzymes (Hemati et al., 2020; Liu et al., 2019). In addition to anti-inflammation, anti-oxidation, biological rhythms resynchronization, and sleep induction, melatonin has multiple biological impacts, including apoptosis induction and immunomodulation (Carlberg, 2000; Pourhanifeh et al., 2020). Crucial effects of melatonin such as oncostatic properties are mediated through receptor-independent and receptor-dependent mechanisms (Srinivasan et al., 2008). The MT1 receptor is thought to be implicated in melatonin suppressive effects in mammalian brains to modulate brain functions; this type of receptor is primarily distributed in the Androsterone retina, skin, Androsterone liver, hypothalamus suprachiasmatic nuclei, and pars-tuberalis of the pituitary gland (Carbajo\Pescador et al., 2011; Reiter, 1991). The MT2 receptor is involved in phase-shifting circadian activity rhythms; this receptor is mainly located in the retina, vessels of extremities, and osteoblasts. Receptor-independent mechanisms of melatonin are associated with the prevention of tumor metabolism, circadian disruption, and suppression of migration and angiogenesis (Hill et al., 2015; Srinivasan et al., 2008). Melatonin easily penetrates into cells and exerts diverse potential impacts through interacting with intracellular and cell surface receptors, or direct scavenging free radicals (Hosseinzadeh et al., 2018b); these actions of melatonin result in the regulation of a broad range of pathways which are important Rabbit polyclonal to Fyn.Fyn a tyrosine kinase of the Src family.Implicated in the control of cell growth.Plays a role in the regulation of intracellular calcium levels.Required in brain development and mature brain function with important roles in the regulation of axon growth, axon guidance, and neurite extension.Blocks axon outgrowth and attraction induced by NTN1 by phosphorylating its receptor DDC.Associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein.Three alternatively spliced isoforms have been described.Isoform 2 shows a greater ability to mobilize cytoplasmic calcium than isoform 1.Induced expression aids in cellular transformation and xenograft metastasis. for cellular actions, including cell-to-cell communication, DNA damage responses, and cellular metabolism (Luchetti et al., 2010). In various pathological conditions, melatonin is able to regulate autophagy process. Autophagy is an intracellular degradation system delivering cytoplasmic constituents to the lysosome (Dehdashtian et al., 2018). Furthermore, the neuroprotective (Alghamdi, 2018) and cardioprotective (Lochner et al., 2018) abilities of melatonin have previously been demonstrated. Melatonin has beneficial properties in female reproduction (Olcese, 2020) and male fertility (Kratz and Piwowar, 2017). Moreover, melatonin plays essential roles in controlling metabolic diseases (Cardinali and Hardeland, 2017; Karamitri and Jockers, 2019), ocular diseases (Scuderi et al., 2019), and rheumatologic diseases (Jahanban-Esfahlan et al., 2018). Regarding these potentials, melatonin is suggested to have the ability of restricting viral infections. 3.?Melatonin and viral infections: cellular signaling and therapeutic aspects 3.1. Melatonin and respiratory syncytial virus Respiratory syncytial virus (RSV), a negative strand RNA virus, belongs to the family Pneumoviridae and causes infection leading to hospitalization of over 3.2 million children under Androsterone 5 years of age each year (Gil-Prieto et al., 2015). Furthermore, this virus causes the infection of lower respiratory tract in adults; the immune-compromised and elderly people are prone to severe disease (Falsey et al., 2005, 2014; Openshaw et al., 2017). Respiratory syncytial virus infection is responsible for.