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Assessing the antiviral potential of melatonin: A comprehensive systematic review

Alomari et al., Reviews in Medical Virology, doi:10.1002/rmv.2499

Dec 2023

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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.

5,200+ studies for 112 treatments. c19early.org

Review of the antiviral potential of melatonin through analysis of In Silico, In Vitro, animal, and clinical studies. Authors identify 20 relevant studies showing evidence that melatonin has strong antiviral properties. In silico studies show melatonin as a candidate against SARS-CoV-2 that could reduce respiratory responses. Cell culture experiments reveal multifaceted antiviral effects on respiratory syncytial virus and other viruses. Animal studies demonstrate reduced mortality and viral replication with melatonin treatment of infections including COVID-19.

Reviews covering melatonin for COVID-19 include1-23.

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1. Sanduzzi Zamparelli et al., Immune-Boosting and Antiviral Effects of Antioxidants in COVID-19 Pneumonia: A Therapeutic Perspective, Life, doi:10.3390/life15010113.mdpi.com, doi.org.

2. Xie et al., The role of reactive oxygen species in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection-induced cell death, Cellular & Molecular Biology Letters, doi:10.1186/s11658-024-00659-6.biomedcentral.com, doi.org.

3. Zhao et al., Melatonin Potentially Acts as a Widely-Acting Protective Tool in COVID-19, Medicine Research, doi:10.21127/yaoyimr20240006.medicineresearch.org, doi.org.

4. Yehia et al., Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration, Molecular Neurodegeneration, doi:10.1186/s13024-024-00728-6.biomedcentral.com, doi.org.

5. Chacin-Bonilla et al., Melatonin and viral infections: A review focusing on therapeutic effects and SARS-CoV-2, Melatonin Research, doi:10.32794/mr112500168.melatonin-research.net, doi.org.

6. Lempesis et al., A mid‑pandemic night's dream: Melatonin, from harbinger of anti‑inflammation to mitochondrial savior in acute and long COVID‑19 (Review), International Journal of Molecular Medicine, doi:10.3892/ijmm.2024.5352.spandidos-publications.com, doi.org.

7. Alomari et al., Assessing the antiviral potential of melatonin: A comprehensive systematic review, Reviews in Medical Virology, doi:10.1002/rmv.2499.wiley.com, doi.org.

8. Donzelli, A., Neglected Effective Early Therapies against COVID-19: Focus on Functional Foods and Related Active Substances. A Review, MDPI AG, doi:10.20944/preprints202312.1178.v1.preprints.org, doi.org.

9. Langen, M., Melatonin - the Hormone of Both Sun and Darkness - Protects Your Health and Can Save Your Life, Rounding The Earth, roundingtheearth.substack.com/p/melatonin-the-hormone-of-both-sun.substack.com.

10. Hosseinzadeh et al., Melatonin effect on platelets and coagulation: Implications for a prophylactic indication in COVID-19, Life Sciences, doi:10.1016/j.lfs.2022.120866.sciencedirect.com, doi.org.

11. Loh et al., Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19, International Journal of Molecular Sciences, doi:10.3390/ijms23158122.mdpi.com, doi.org.

12. Reiter et al., Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection, Cellular and Molecular Life Sciences, doi:10.1007/s00018-021-04102-3.springer.com, doi.org.

13. Tan et al., Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality, Life Sciences, doi:10.1016/j.lfs.2022.120368.sciencedirect.com, doi.org.

14. Behl et al., CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target, Science of The Total Environment, doi:10.1016/j.scitotenv.2021.152072.sciencedirect.com, doi.org.

15. Castle et al., Implications for Systemic Approaches to COVID-19: Effect Sizes of Remdesivir, Tocilizumab, Melatonin, Vitamin D3, and Meditation, Journal of Inflammation Research, doi:10.2147/JIR.S323356.dovepress.com, doi.org.

16. Ramos et al., The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy, Antioxidants, doi:10.3390/antiox10071152.mdpi.com, doi.org.

17. Camp et al., Melatonin interferes with COVID-19 at several distinct ROS-related steps, Journal of Inorganic Biochemistry, doi:10.1016/j.jinorgbio.2021.111546.sciencedirect.com, doi.org.

18. Cross et al., Melatonin for the Early Treatment of COVID-19: A Narrative Review of Current Evidence and Possible Efficacy, Endocrine Practice, doi:10.1016/j.eprac.2021.06.001.sciencedirect.com, doi.org.

19. DiNicolantonio et al., Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections, Open Heart, doi:10.1136/openhrt-2020-001568.bmj.com, doi.org.

20. Reiter (B) et al., Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19, Frontiers in Medicine, doi:10.3389/fmed.2020.00226.frontiersin.org, doi.org.

21. Charaa et al., Prophylactic Treatment Protocol against the Severity of COVID-19 Using Melatonin, SSRN, doi:10.2139/ssrn.3601861.ssrn.com, doi.org.

22. Shneider et al., Can melatonin reduce the severity of COVID-19 pandemic?, International Reviews of Immunology, doi:10.1080/08830185.2020.1756284.tandfonline.com, doi.org.

23. Zhang et al., COVID-19: Melatonin as a potential adjuvant treatment, Life Sciences, doi:10.1016/j.lfs.2020.117583.sciencedirect.com, doi.org.

Alomari et al., 21 Dec 2023, peer-reviewed, 6 authors.

This Paper Melatonin All

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In silico ' 'studies identify melatonin as a candidate against SARS‐CoV‐2, reducing cytokine storm‐related ' 'respiratory responses. Cell culture experiments reveal its multifaceted effects on different ' 'viruses including respiratory syncytial virus, anti‐dengue virus, transmissible ' 'gastroenteritis virus, and encephalomyocarditis virus. Animal studies show melatonin reduces ' 'mortality and viral replication in various infections such as Venezuelan equine ' 'encephalomyelitis and COVID‐19. Clinical trials show how it could be evaluated, but with no ' 'conclusive evidence of efficacy and safety so far from large, double‐blind placebo‐controlled ' 'trials. These insights showcase the potential of melatonin as a versatile antiviral agent ' 'with immunomodulatory, antioxidant, anti‐inflammatory and antiviral properties. In summary, ' "our review highlights melatonin's promising antiviral properties across diverse settings. 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