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Therapeutic potential of melatonin and melatonergic drugs on K18-hACE2 mice infected with SARS-CoV-2

Cecon et al., Journal of Pineal Research, doi:10.1111/jpi.12772
Sep 2021  
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Melatonin for COVID-19
10th treatment shown to reduce risk in December 2020
*, now known with p = 0.0000002 from 18 studies.
Lower risk for mortality, ventilation, and recovery.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments.
Study of melatonin and melatonergic compounds with mice expressing the human ACE2 receptor (K18-hACE2). Daily administration of melatonin, agomelatine or ramelteon delayed the occurrence of severe clinical outcome with improvement of survival, especially with high melatonin dose.
3 preclinical studies support the efficacy of melatonin for COVID-19:
Cecon et al., 29 Sep 2021, peer-reviewed, 11 authors.
This PaperMelatoninAll
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, PhD Ralf Jockers, Julie Dam
Journal of Pineal Research, doi:10.1111/jpi.12772
Word count: 181 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.
AUTHOR CONTRIBUTIONS Conceptualization, E.C., J.D., and R. COMPETING INTERESTS The authors declare no competing interest.
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