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Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

Loh et al., International Journal of Molecular Sciences, doi:10.3390/ijms23158122

Jul 2022

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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.

4,100+ studies for 60+ treatments. c19early.org

Review of melatonin for viral infections and post-infection sequelae. The SARS-CoV-2 virus can cause oxidative stress, mitochondrial dysfunction, LINE1 derepression, and changes to m6A RNA modifications. These effects can increase viral replication and suppress host immune responses. Melatonin employs antioxidant and non-antioxidant mechanisms to modulate viral phase separation, restore mitochondrial function, suppress LINE1 derepression, and regulate m6A modifications. Through these diverse actions, melatonin may inhibit acute viral infection and replication, as well as prevent post-infection complications. The authors suggest melatonin could be an important therapeutic adjuvant for SARS-CoV-2 infection and post-infection recovery.

Reviews covering melatonin for COVID-19 include Alomari, Behl, Camp, Castle, Charaa, Cross, DiNicolantonio, Hosseinzadeh, Langen, Lempesis, Loh, Ramos, Reiter, Reiter (B), Shneider, Tan, Yehia, Zhang.

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1. 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.

2. 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.

3. 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.

4. 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.

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

6. 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.

7. 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.

8. 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.

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. 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.

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. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

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

Loh et al., 23 Jul 2022, peer-reviewed, 2 authors. Contact: reiter@uthscsa.edu (corresponding author), lohdoris23@gmail.com.

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