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    Melatonin treatment of infected mice decreases COVID-19

    Teams Ralf Jockers and Morgane Bomsel

    Therapeutic potential of melatonin and derived drugs on COVID-19 mouse model infected with SARS-CoV-2


    The study conducted by the team of Erika Cecon / Julie Dam / Ralf Jockers in collaboration with the teams of Morgane Bomsel and Sophie Le Poder / Bernard Klonjkowski (National Veterinary School of Alfort, Maisons-Alfort) highlighted the therapeutic potential of melatonin and its derivative drugs on an animal model of COVID-19 infected with SARS-CoV-2. This work, the results of which were published in the Journal of Pineal Research, was funded by the National Research Agency (ANR-RA-COVID-19: ANR-20-COV4-0001).


    This study has to be placed in the context of the SARS-CoV-2 pandemic in which the treatment options for combating SARS-CoV-2 infection still need to be investigated and rapidly identified. To this end, the research team of E Cecon, J Dam and R Jockers, in collaboration with their partners, evaluated the impact of melatonin and melatonin receptor-targeting drugs (agomelatine and ramelteon) in a preclinical mouse model of COVID-19. This study was prompted by multiple claims in the literature suggesting that melatonin may help reduce symptoms of COVID-19; however, experimental data was totally lacking.

    Melatonin, often referred to as the “hormone of darkness”, is produced in a small brain region, and its secretion, inhibited in the presence of light, is stimulated at dark. This hormone regulates our circadian rhythms, such as the sleep/wake cycle. Melatonin and its derivative drugs are currently prescribed to treat jet lag, certain sleep disorders, or certain major depressive disorders.

    The researchers studied the therapeutic potential of melatonin and derivatives in a mouse model (human K18-ACE2) where the main receptor for SARS-CoV-2 in mice, ACE2, is replaced by its human counterpart, for its high susceptibility to intranasal infection with SARS-CoV-2. This experimental model summarizes the symptoms seen in patients with severe COVID-19, including lung damage, respiratory distress, cytokine storm, and mortality.




    Legend: Treatment by melatonin (2 doses), agomelatine (AgoMLT) and ramelteon (RML) decreases the exacerbated levels of type I and III interferons in the lungs of infected mice, 7 days after infection with SARS-CoV- 2





    The study showed that the daily administration of melatonin, agomelatine or ramelteon, and in particular the highest dose of melatonin, delays the onset of clinical symptoms, increases the survival of infected mice and limits exacerbated levels of interferons in the lungs that are believed to help improving the symptoms. The promising data from this work should encourage new clinical studies on COVID-19, focusing specifically on a combined therapeutic treatment associating melatonin.



    Erika CeconCharlotte IzabelleSophie Le PoderFernando RealAiwei ZhuLy TuMaria Rosa GhignaBernard KlonjkowskiMorgane BomselRalf JockersJulie DamTherapeutic potential of melatonin and melatonergic drugs on K18-hACE2 mice infected with SARS-CoV-2J Pineal Res202100:e12772.


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