Multiple actions of melatonin in reducing viral pathophysiologies

Abstract

Viral infections lead to significant morbidity and mortality while the effective therapeutic approaches are lacking. Melatonin (MEL) (N-acetyl-5-methoxytryptamine) is a pleiotropic molecule that has a variety of functions, including the antiviral properties. It is a potent antioxidant, anti-inflammatory agent, a stimulator of immune functions, and regulator of apoptosis. These effects support the use of MEL in viral infections, which are often associated with excessive inflammatory responses and elevated oxidative stress. The virus- and cytokine- storm-driven control of the pineal and mitochondrial melatonergic pathway regulates immune responses and increases gut dysbiosis, suppressing levels of the short-chain fatty acid, butyrate, and increasing circulating lipopolysaccharides, stimulating viral replication and host symptoms severity. MEL has a contrasting role in controlling the pathophysiological effects of various viruses due to its chronobiotic, antioxidant and anti-inflammatory actions. Several recent preclinical and clinical studies have documented a robust protective effect of MEL against viral infections, including COVID-19 and it has emerged as an excellent candidate for protection against an array of different viruses. This review summarizes available data on the beneficial effects of MEL on viral pathophysiological actions, and also discusses and highlights likely evidence-based therapeutic applications.