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Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection

Reiter et al., Cellular and Molecular Life Sciences, doi:10.1007/s00018-021-04102-3
Feb 2022  
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Melatonin for COVID-19
10th 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. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19early.org
Review of the clinical evidence and mechanisms of action supporting the use of melatonin for COVID-19.
Reviews covering melatonin for COVID-19 include1-20.
Reiter et al., 20 Feb 2022, peer-reviewed, 11 authors.
This PaperMelatoninAll
Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection
Russel J Reiter, Ramaswamy Sharma, Fedor Simko, Alberto Dominguez-Rodriguez, Jan Tesarik, Richard L Neel, Andrzej T Slominski, Konrad Kleszczynski, Verna M Martin-Gimenez, Walter Manucha, Daniel P Cardinali
Cellular and Molecular Life Sciences, doi:10.1007/s00018-021-04102-3
Numerous pharmaceutical drugs have been repurposed for use as treatments for COVID-19 disease. These drugs have not consistently demonstrated high efficacy in preventing or treating this serious condition and all have side effects to differing degrees. We encourage the continued consideration of the use of the antioxidant and anti-inflammatory agent, melatonin, as a countermeasure to a SARS-CoV-2 infection. More than 140 scientific publications have identified melatonin as a likely useful agent to treat this disease. Moreover, the publications cited provide the rationale for the use of melatonin as a prophylactic agent against this condition. Melatonin has pan-antiviral effects and it diminishes the severity of viral infections and reduces the death of animals infected with numerous different viruses, including three different coronaviruses. Network analyses, which compared drugs used to treat SARS-CoV-2 in humans, also predicted that melatonin would be the most effective agent for preventing/treating COVID-19. Finally, when seriously infected COVID-19 patients were treated with melatonin, either alone or in combination with other medications, these treatments reduced the severity of infection, lowered the death rate, and shortened the duration of hospitalization. Melatonin's ability to arrest SARS-CoV-2 infections may reduce health care exhaustion by limiting the need for hospitalization. Importantly, melatonin has a high safety profile over a wide range of doses and lacks significant toxicity. Some molecular processes by which melatonin resists a SARS-CoV-2 infection are summarized. The authors believe that all available, potentially beneficial drugs, including melatonin, that lack toxicity should be used in pandemics such as that caused by SARS-CoV-2.
Author contributions Before writing began, all co-authors discussed the publications related to this report. The final selection of papers to be covered in the report was done by RJR and RS. The initial draft of the paper was written by RJR and then reviewed by all co-authors. The suggestions of all co-authors were incorporated into the final version of the review by RJR. All co-authors read and approved the final version of the manuscript. Declarations Conflict of interest The authors declare no conflicts of interest. Ethical approval Not applicable. Consent to participate Not applicable. Consent for publication Not applicable. Ethical approval Not applicable. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat..
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These drugs have not consistently demonstrated ' 'high efficacy in preventing or treating this serious condition and all have side effects to ' 'differing degrees. We encourage the continued consideration of the use of the antioxidant and ' 'anti-inflammatory agent, melatonin, as a countermeasure to a SARS-CoV-2 infection. More than ' '140 scientific publications have identified melatonin as a likely useful agent to treat this ' 'disease. Moreover, the publications cited provide the rationale for the use of melatonin as a ' 'prophylactic agent against this condition. Melatonin has pan-antiviral effects and it ' 'diminishes the severity of viral infections and reduces the death of animals infected with ' 'numerous different viruses, including three different coronaviruses. Network analyses, which ' 'compared drugs used to treat SARS-CoV-2 in humans, also predicted that melatonin would be the ' 'most effective agent for preventing/treating COVID-19. Finally, when seriously infected ' 'COVID-19 patients were treated with melatonin, either alone or in combination with other ' 'medications, these treatments reduced the severity of infection, lowered the death rate, and ' 'shortened the duration of hospitalization. Melatonin’s ability to arrest SARS-CoV-2 ' 'infections may reduce health care exhaustion by limiting the need for hospitalization. ' 'Importantly, melatonin has a high safety profile over a wide range of doses and lacks ' 'significant toxicity. Some molecular processes by which melatonin resists a SARS-CoV-2 ' 'infection are summarized. The authors believe that all available, potentially beneficial ' 'drugs, including melatonin, that lack toxicity should be used in pandemics such as that ' 'caused by SARS-CoV-2.</jats:p>', 'DOI': '10.1007/s00018-021-04102-3', 'type': 'journal-article', 'created': {'date-parts': [[2022, 2, 20]], 'date-time': '2022-02-20T19:02:23Z', 'timestamp': 1645383743000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 2, 'title': ['Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection'], 'prefix': '10.1007', 'volume': '79', 'author': [ { 'ORCID': 'http://orcid.org/0000-0001-6763-4225', 'authenticated-orcid': False, 'given': 'Russel J.', 'family': 'Reiter', 'sequence': 'first', 'affiliation': []}, {'given': 'Ramaswamy', 'family': 'Sharma', 'sequence': 'additional', 'affiliation': []}, {'given': 'Fedor', 'family': 'Simko', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Alberto', 'family': 'Dominguez-Rodriguez', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jan', 'family': 'Tesarik', 'sequence': 'additional', 'affiliation': []}, {'given': 'Richard L.', 'family': 'Neel', 'sequence': 'additional', 'affiliation': []}, {'given': 'Andrzej T.', 'family': 'Slominski', 'sequence': 'additional', 'affiliation': []}, {'given': 'Konrad', 'family': 'Kleszczynski', 'sequence': 'additional', 'affiliation': []}, {'given': 'Verna M.', 'family': 'Martin-Gimenez', 'sequence': 'additional', 'affiliation': []}, {'given': 'Walter', 'family': 'Manucha', 'sequence': 'additional', 'affiliation': []}, {'given': 'Daniel P.', 'family': 'Cardinali', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2022, 2, 20]]}, 'reference': [ { 'issue': '3', 'key': '4102_CR1', 'doi-asserted-by': 'publisher', 'first-page': '311', 'DOI': '10.32794/mr11250064', 'volume': '3', 'author': 'DP Cardinali', 'year': '2020', 'unstructured': 'Cardinali DP (2020) High doses of melatonin as a potential therapeutic ' 'tool for the neurologic sequels of covid-19 infection. 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