Ramos Alonso, EvaLópez Muñoz, FranciscoGil Martín, EmilioEgea, JavierÁlvarez Merz, IrisPainuli, SakshiSemwal, PrabhakarMartins, NatáliaHernández Guijo, Jesús MRomero Martínez, Manuel Alejandro2025-05-222025-05-222021-07-20Ramos, E., López-Muñoz, F., Gil-Martín, E., Egea, J., Álvarez-Merz, I., Painuli, S., Semwal, P., Martins, N., Hernández-Guijo, J. M., & Romero, A. (2021). The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy. Antioxidants (Basel, Switzerland), 10(7), 1152. https://doi.org/10.3390/antiox100711522076-392110.3390/antiox10071152https://hdl.handle.net/20.500.14352/120431Author Contributions: Conceptualization, methodology, writing original draft preparation, review and editing, supervision, and funding acquisition, A.R.; writing—review and editing, data curation, and tables, E.R.; review and editing, F.L.-M.; writing—original draft preparation, review and editing, data curation, and visualization, E.G.-M.; review and editing, J.E.; data curation, I.Á.-M.; review and editing and data curation, S.P.; review and editing and data curation, P.S.; conceptualization, writing— original draft preparation and review and editing, N.M.; conceptualization, writing—original draft preparation, review and editing, and supervision, J.M.H.-G. All authors have read and agreed to the published version of the manuscript.Viral infections constitute a tectonic convulsion in the normophysiology of the hosts. The current coronavirus disease 2019 (COVID-19) pandemic is not an exception, and therefore the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, like any other invading microbe, enacts a generalized immune response once the virus contacts the body. Melatonin is a systemic dealer that does not overlook any homeostasis disturbance, which consequently brings into play its cooperative triad, antioxidant, anti-inflammatory, and immune-stimulant backbone, to stop the infective cycle of SARS-CoV-2 or any other endogenous or exogenous threat. In COVID-19, the corporal propagation of SARS-CoV-2 involves an exacerbated oxidative activity and therefore the overproduction of great amounts of reactive oxygen and nitrogen species (RONS). The endorsement of melatonin as a possible protective agent against the current pandemic is indirectly supported by its widely demonstrated beneficial role in preclinical and clinical studies of other respiratory diseases. In addition, focusing the therapeutic action on strengthening the host protection responses in critical phases of the infective cycle makes it likely that multi-tasking melatonin will provide multi-protection, maintaining its efficacy against the virus variants that are already emerging and will emerge as long as SARS-CoV-2 continues to circulate among us.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://doi.org/10.3390/antiox1007115234356384open access61SARS-CoV-2Adjuvant therapyAntioxidantCircadian rhythmsClinical trialsInflammationMelatoninMitochondriaSafetyCiencias Biomédicas32 Ciencias Médicas