ER stress and autophagy induced by SARS-CoV-2: The targets for melatonin treatment

Abstract

Coronavirus disease 19 (COVID-19) is a viral disease caused by the new coronavirus SARS-CoV-2. Like other coronaviral infections, SARS-CoV-2 causes oxidative and ER stress triggering cellular response pathways, mainly PERK and IRE1 branches of the UPR. This excessive oxidative stress and the increasing of unfolded and misfolded proteins induce autophagy. Once this process is triggered, the blockage of the fusion of autophagosomes and lysosomes induced by virus leads to an incomplete autophagy. Double-membraned vesicles, which create a membranous support for viral RNA replication complexes, are formed. Melatonin is a pleiotropic molecule, which reduces oxidative and ER stress, regulates immune system, and modulates autophagy pathway. Thus, melatonin reinforces UPR and unlocks autophagy blockage, allowing autophagosomes to bind to lysosomes, completing the process of autophagy and decreasing viral replication capacity. Based on these activities of melatonin the recommendation of melatonin for patients with COVID-19 should be seriously considered, especially in elderlies and patients with different comorbidities, which are the highest risk population for serious cases.