Therapeutic potential of melatonin and melatonergic drugs on K18-hACE2 mice infected with SARS-CoV-2.
Erika Cecon, Charlotte Izabelle, Sophie Le Poder, Fernando Real, Aiwei Zhu, Ly Tu, Maria Rosa Ghigna, Bernard Klonjkowski, Morgane Bomsel, Ralf Jockers, Julie Dam
Author Information
Erika Cecon: Institut Cochin, INSERM, CNRS, Université de Paris, Paris, France. ORCID
Charlotte Izabelle: Institut Cochin, INSERM, CNRS, Université de Paris, Paris, France.
Sophie Le Poder: UMR Virologie, INRAE, ANSES, École Nationale Vétérinaire d'Alfort, Maisons-Alfort, France. ORCID
Fernando Real: Institut Cochin, INSERM, CNRS, Université de Paris, Paris, France. ORCID
Aiwei Zhu: Institut Cochin, INSERM, CNRS, Université de Paris, Paris, France.
Ly Tu: School of Medicine Le Kremlin-Bicêtre, Hôpital Marie Lannelongue, INSERM UMRS 999, Université Paris-Saclay, Le Plessis-Robinson, France. ORCID
Maria Rosa Ghigna: School of Medicine Le Kremlin-Bicêtre, Hôpital Marie Lannelongue, INSERM UMRS 999, Université Paris-Saclay, Le Plessis-Robinson, France. ORCID
Bernard Klonjkowski: UMR Virologie, INRAE, ANSES, École Nationale Vétérinaire d'Alfort, Maisons-Alfort, France. ORCID
Morgane Bomsel: Institut Cochin, INSERM, CNRS, Université de Paris, Paris, France. ORCID
Ralf Jockers: Institut Cochin, INSERM, CNRS, Université de Paris, Paris, France. ORCID
Julie Dam: Institut Cochin, INSERM, CNRS, Université de Paris, Paris, France. ORCID
As the COVID-19 pandemic grows, several therapeutic candidates are being tested or undergoing clinical trials. Although prophylactic vaccination against SARS-CoV-2infection 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-2infection. 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.
