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Antiviral Effect of Melatonin on Caco-2 Cell Organoid Culture: Trick or Treat?

Šeškutė et al., International Journal of Molecular Sciences, doi:10.3390/ijms252211872
Nov 2024  
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Melatonin for COVID-19
11th treatment shown to reduce risk in December 2020, now with p = 0.0000002 from 18 studies.
Lower risk for mortality, ventilation, and recovery.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19early.org
In Vitro study showing that melatonin exhibits antiviral properties in gastrointestinal epithelial cells through modulation of type III interferon responses and cellular protection. Authors found that melatonin's effects varied based on timing of administration, with pretreatment (1-10 μM) enhancing cell proliferation and reducing apoptosis, while post-infection treatment preserved tissue structure and reduced inflammatory cytokine production. Using a Caco-2 cell organoid model, melatonin treatment after viral simulation increased IFNLR1 expression while reducing IFNλ1 and STAT1-3 protein levels, suggesting potential benefits for controlling excessive inflammatory responses. Authors stimulated viral inflammation using a TLR3 receptor agonist rather than live virus infection. While not specifically analyzing SARS-CoV-2, the findings support previous research showing melatonin's potential therapeutic value in COVID-19 through its immunomodulatory and tissue-protective properties.
6 preclinical studies support the efficacy of melatonin for COVID-19:
Melatonin may restore altered redox homeostasis in COVID-196, modulates type III interferon responses and reduces inflammatory cytokine production in TLR3 receptor agonist stimulated viral inflammation while preserving tissue integrity3, and negatively regulates genes critical for viral entry in lung tissue, including reduced expression of FURIN and components of the CD147 complex, while potentially disrupting TMPRSS2/ACE2-mediated entry mechanisms2. Melatonin reduces oxidative stress, inhibits NET formation, and protects tissues through anti-inflammatory and antioxidant actions7.
Šeškutė et al., 5 Nov 2024, peer-reviewed, 6 authors. Contact: lina.jankauskaite@lsmu.lt (corresponding author), milda.seskute@lsmu.lt, goda.laucaityte@lsmu.lt, mantas.malinauskas@lsmu.lt, dominyka.zukaite@stud.lsmu.lt, ruta.inciuraite@lsmu.lt.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperMelatoninAll
Antiviral Effect of Melatonin on Caco-2 Cell Organoid Culture: Trick or Treat?
Milda Šeškutė, Dominyka Žukaitė, Goda Laucaitytė, Rūta Inčiūraitė, Mantas Malinauskas, Lina Jankauskaitė
International Journal of Molecular Sciences, doi:10.3390/ijms252211872
Melatonin is a hormone naturally produced by the body that has recently been found to have antiviral properties. However, its antiviral mechanisms are not entirely understood. Using Caco-2 cells, we developed a gastrointestinal organoid model to investigate the impact of melatonin on cellular organoid culture response to Poly I:C-induced viral inflammation in the gastrointestinal tract. Melatonin was found to have different effect when applied as a pretreatment before the induction of viral inflammation or as a treatment after it. Melatonin pretreatment after Poly I:C stimulation did not protect organoids from size reduction but enhanced cell proliferation, especially when lower (1 and 10 µM) melatonin concentrations were used. On the other hand, treatment with melatonin after the induction of viral inflammation helped to maintain the size of the organoids while reducing cell proliferation. In pretreated cells, reduced IFNLR1 expression was found, while melatonin treatment increased IFNLR1 expression and reduced the production of viral cytokines, such as IFNλ1 and STAT1-3, but did not prevent from apoptosis. The findings of this study emphasize the importance of type III IFNs in antiviral defense in epithelial gastrointestinal cells and shed more light on the antiviral properties of melatonin as a potential therapeutic substance.
Author Contributions: Investigations, M.Š., D.Ž., G.L., R.I., M.M. and L.J.; data analysis, M.Š., D.Ž. and L.J., writing-original draft preparation, M.Š. and D.Ž.; writing-review and editing, L.J.; supervision, L.J.; funding acquisition, L.J. All authors have read and agreed to the published version of the manuscript. Conflicts of Interest: The authors declare no conflicts of interest.
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