Abstract : As the COVID-19 pandemic grows, several therapeutic candidates are being tested or undergoing clinical trials. Although prophylactic vaccination against SARS-CoV-2 infection has been shown to be effective, no definitive treatment exists to date in the event of infection. The rapid spread of infection by SARS-CoV-2 and its variants fully warrants the continued evaluation of drug treatments for COVID-19, especially in the context of repurposing of already available and safe drugs. Here, we explored the therapeutic potential of melatonin and melatonergic compounds in attenuating COVID-19 pathogenesis in mice expressing human ACE2 receptor (K18-hACE2), strongly susceptible to SARS-CoV-2 infection. Daily administration of melatonin, agomelatine, or ramelteon delays the occurrence of severe clinical outcome with improvement of survival, especially with high melatonin dose. Although no changes in most lung inflammatory cytokines are observed, treatment with melatonergic compounds limits the exacerbated local lung production of type I and type III interferons, which is likely associated with the observed improved symptoms in treated mice. The promising results from this preclinical study should encourage studies examining the benefits of repurposing melatonergic drugs to treat COVID-19 and related diseases in humans.
Résumé : L'étude menée par l'équipe de Erika Cecon / Julie Dam/ Ralf Jockers, en collaboration avec les équipes de Morgane Bomsel et de Sophie Le Poder / Bernard Klonjkowski (École Nationale Vétérinaire d'Alfort, Maisons-Alfort) a mis en évidence le potentiel thérapeutique de la mélatonine et de ses médicaments dérivés sur un modèle animal de la COVID-19, infecté avec le SARS-CoV-2. Ce travail, dont les résultats ont été publiés dans le Journal of Pineal Research, a été financé par l'Agence Nationale de la Recherche (ANR-RA-COVID-19: ANR-20-COV4-0001).