Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections

DOI record: { "DOI": "10.1136/openhrt-2020-001568", "ISSN": [ "2053-3624" ], "URL": "http://dx.doi.org/10.1136/openhrt-2020-001568", "abstract": "<jats:p>A recent retrospective study has provided evidence that COVID-19 infection may be notably less common in those using supplemental melatonin. It is suggested that this phenomenon may reflect the fact that, via induction of silent information regulator 1 (Sirt1), melatonin can upregulate K63 polyubiquitination of the mitochondrial antiviral-signalling protein, thereby boosting virally mediated induction of type 1 interferons. Moreover, Sirt1 may enhance the antiviral efficacy of type 1 interferons by preventing hyperacetylation of high mobility group box 1 (HMGB1), enabling its retention in the nucleus, where it promotes transcription of interferon-inducible genes. This nuclear retention of HMGB1 may also be a mediator of the anti-inflammatory effect of melatonin therapy in COVID-19—complementing melatonin’s suppression of nuclear factor kappa B activity and upregulation of nuclear factor erythroid 2-related factor 2. If these speculations are correct, a nutraceutical regimen including vitamin D, zinc and melatonin supplementation may have general utility for the prevention and treatment of RNA virus infections, such as COVID-19 and influenza.</jats:p>", "alternative-id": [ "10.1136/openhrt-2020-001568" ], "author": [ { "ORCID": "http://orcid.org/0000-0002-7888-1528", "affiliation": [], "authenticated-orcid": false, "family": "DiNicolantonio", "given": "James J", "sequence": "first" }, { "affiliation": [], "family": "McCarty", "given": "Mark", "sequence": "additional" }, { "affiliation": [], "family": "Barroso-Aranda", "given": "Jorge", "sequence": "additional" } ], "container-title": "Open Heart", "container-title-short": "Open Heart", "content-domain": { "crossmark-restriction": true, "domain": [ "bmj.com" ] }, "created": { "date-parts": [ [ 2021, 3, 19 ] ], "date-time": "2021-03-19T16:17:53Z", "timestamp": 1616170673000 }, "deposited": { "date-parts": [ [ 2021, 3, 19 ] ], "date-time": "2021-03-19T16:18:17Z", "timestamp": 1616170697000 }, "indexed": { "date-parts": [ [ 2024, 3, 27 ] ], "date-time": "2024-03-27T02:29:26Z", "timestamp": 1711506566345 }, "is-referenced-by-count": 9, "issue": "1", "issued": { "date-parts": [ [ 2021, 3 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2021, 3, 19 ] ] }, "published-print": { "date-parts": [ [ 2021, 3 ] ] } }, "language": "en", "license": [ { "URL": "http://creativecommons.org/licenses/by-nc/4.0/", "content-version": "unspecified", "delay-in-days": 18, "start": { "date-parts": [ [ 2021, 3, 19 ] ], "date-time": "2021-03-19T00:00:00Z", "timestamp": 1616112000000 } } ], "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1136/openhrt-2020-001568", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "239", "original-title": [], "page": "e001568", "prefix": "10.1136", "published": { "date-parts": [ [ 2021, 3 ] ] }, "published-online": { "date-parts": [ [ 2021, 3, 19 ] ] }, "published-print": { "date-parts": [ [ 2021, 3 ] ] }, "publisher": "BMJ", "reference": [ { "article-title": "Melatonin is significantly associated with survival of intubated COVID-19 patients", "author": "Ramlall", "journal-title": "medRxiv", "key": "2021031909151460000_8.1.e001568.1", "year": "2020" }, { "DOI": "10.1096/fj.15-273656", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.2" }, { "DOI": "10.1111/jpi.12525", "article-title": "Melatonin and inflammation-Story of a double-edged blade", "author": "Hardeland", "doi-asserted-by": "crossref", "journal-title": "J Pineal Res", "key": "2021031909151460000_8.1.e001568.3", "volume": "65", "year": "2018" }, { "DOI": "10.3390/molecules15107266", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.4" }, { "DOI": "10.1371/journal.pbio.3000970", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.5" }, { "DOI": "10.1161/CIRCRESAHA.116.307708", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.6" }, { "DOI": "10.1186/s40885-020-00147-x", "article-title": "The angiotensin-converting enzyme 2 (ACE2) receptor in the prevention and treatment of COVID-19 are distinctly different paradigms", "author": "McLachlan", "doi-asserted-by": "crossref", "first-page": "14", "journal-title": "Clin Hypertens", "key": "2021031909151460000_8.1.e001568.7", "volume": "26", "year": "2020" }, { "DOI": "10.1002/hep.26992", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.8" }, { "DOI": "10.1073/pnas.1800431115", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.9" }, { "DOI": "10.1016/j.vetmic.2017.09.022", "article-title": "RIG-1 and MDA-5 signaling pathways contribute to IFN-β production and viral replication in porcine circovirus virus type 2-infected PK-15 cells in vitro", "author": "Huang", "doi-asserted-by": "crossref", "first-page": "36", "journal-title": "Vet Microbiol", "key": "2021031909151460000_8.1.e001568.10", "volume": "211", "year": "2017" }, { "DOI": "10.15252/embj.2019102075", "article-title": "TRAF3IP3 mediates the recruitment of TRAF3 to MAVS for antiviral innate immunity", "author": "Zhu", "doi-asserted-by": "crossref", "journal-title": "Embo J", "key": "2021031909151460000_8.1.e001568.11", "volume": "38", "year": "2019" }, { "DOI": "10.1038/ni.3641", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.12" }, { "DOI": "10.1016/j.molcel.2020.06.020", "article-title": "Acetylation-Dependent deubiquitinase OTUD3 controls MAVS activation in innate antiviral immunity", "author": "Zhang", "doi-asserted-by": "crossref", "first-page": "304", "journal-title": "Mol Cell", "key": "2021031909151460000_8.1.e001568.13", "volume": "79", "year": "2020" }, { "DOI": "10.1074/jbc.M509329200", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.14" }, { "DOI": "10.1111/jnc.15258", "doi-asserted-by": "crossref", "key": "2021031909151460000_8.1.e001568.15", "unstructured": "Deng Hong‐Ji , Zhou Chen‐Hui , Huang Li‐Tian , et al . Activation of silent information regulator 1 exerts a neuroprotective effect after intracerebral hemorrhage by deacetylating NF‐κB/p65. J Neurochem 2020.doi:10.1111/jnc.15258" }, { "DOI": "10.1073/pnas.092133199", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.16" }, { "DOI": "10.1038/srep42998", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.17" }, { "DOI": "10.1038/mi.2017.24", "article-title": "BMAL1 links the circadian clock to viral airway pathology and asthma phenotypes", "author": "Ehlers", "doi-asserted-by": "crossref", "first-page": "97", "journal-title": "Mucosal Immunol", "key": "2021031909151460000_8.1.e001568.18", "volume": "11", "year": "2018" }, { "DOI": "10.1093/emboj/cdg516", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.19" }, { "DOI": "10.1371/journal.pone.0041932", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.20" }, { "DOI": "10.1152/ajprenal.00119.2018", "article-title": "SIRT1-mediated HMGB1 deacetylation suppresses sepsis-associated acute kidney injury", "author": "Wei", "doi-asserted-by": "crossref", "first-page": "F20", "journal-title": "Am J Physiol Renal Physiol", "key": "2021031909151460000_8.1.e001568.21", "volume": "316", "year": "2019" }, { "DOI": "10.1097/SHK.0000000000000225", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.22" }, { "DOI": "10.2174/187221412802481784", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.23" }, { "DOI": "10.1159/000508291", "article-title": "HMGB1: a possible crucial therapeutic target for COVID-19?", "author": "Street", "doi-asserted-by": "crossref", "first-page": "73", "journal-title": "Horm Res Paediatr", "key": "2021031909151460000_8.1.e001568.24", "volume": "93", "year": "2020" }, { "DOI": "10.1186/s10020-020-00172-4", "article-title": "Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19?", "author": "Andersson", "doi-asserted-by": "crossref", "first-page": "42", "journal-title": "Mol Med", "key": "2021031909151460000_8.1.e001568.25", "volume": "26", "year": "2020" }, { "DOI": "10.2174/1386207323999200728114927", "article-title": "Could targeting HMGB1 be useful for the clinical management of COVID-19 infection?", "author": "Çelebier", "doi-asserted-by": "crossref", "journal-title": "Comb Chem High Throughput Screen", "key": "2021031909151460000_8.1.e001568.26", "year": "2020" }, { "DOI": "10.1016/j.devcel.2008.02.004", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.27" }, { "DOI": "10.1152/ajpendo.00318.2009", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.28" }, { "DOI": "10.1038/s41598-020-60213-0", "article-title": "Metformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes", "author": "Saenwongsa", "doi-asserted-by": "crossref", "journal-title": "Sci Rep", "key": "2021031909151460000_8.1.e001568.29", "volume": "10", "year": "2020" }, { "DOI": "10.1038/nature06261", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.30" }, { "DOI": "10.3390/ijms20061381", "article-title": "Progress to improve oral bioavailability and beneficial effects of resveratrol", "author": "Chimento", "doi-asserted-by": "crossref", "journal-title": "Int J Mol Sci", "key": "2021031909151460000_8.1.e001568.31", "volume": "20", "year": "2019" }, { "DOI": "10.1155/2015/293524", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.32" }, { "DOI": "10.3390/nu12113361", "article-title": "Evidence regarding vitamin D and risk of COVID-19 and its severity", "author": "Mercola", "doi-asserted-by": "crossref", "journal-title": "Nutrients", "key": "2021031909151460000_8.1.e001568.33", "volume": "12", "year": "2020" }, { "DOI": "10.1089/hs.2020.0137", "article-title": "Association between vitamin D deficiency and COVID-19 incidence, complications, and mortality in 46 countries: an ecological study", "author": "Mariani", "doi-asserted-by": "crossref", "journal-title": "Health Secur", "key": "2021031909151460000_8.1.e001568.34", "year": "2020" }, { "DOI": "10.1016/j.antiviral.2016.11.004", "article-title": "Vitamin D increases the antiviral activity of bronchial epithelial cells in vitro", "author": "Telcian", "doi-asserted-by": "crossref", "first-page": "93", "journal-title": "Antiviral Res", "key": "2021031909151460000_8.1.e001568.35", "volume": "137", "year": "2017" }, { "DOI": "10.1002/jcp.1041420327", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.36" }, { "DOI": "10.1099/vir.0.045013-0", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.37" }, { "DOI": "10.2174/0929867326666190805151654", "article-title": "Antiviral activities of human host defense peptides", "author": "Brice", "doi-asserted-by": "crossref", "first-page": "1420", "journal-title": "Curr Med Chem", "key": "2021031909151460000_8.1.e001568.38", "volume": "27", "year": "2020" }, { "DOI": "10.1016/j.jcv.2010.12.006", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.39" }, { "DOI": "10.3390/nu12040988", "doi-asserted-by": "crossref", "key": "2021031909151460000_8.1.e001568.40", "unstructured": "Grant WB , Lahore H , McDonnell SL , et al . Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients 2020 ;;12:988. April 2. doi:10.3390/nu12040988" }, { "article-title": "Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials", "author": "Jolliffe", "journal-title": "medRxiv", "key": "2021031909151460000_8.1.e001568.41", "year": "2020" }, { "DOI": "10.1016/j.aimed.2020.07.009", "article-title": "Zinc for the prevention and treatment of SARS-CoV-2 and other acute viral respiratory infections: a rapid review", "author": "Arentz", "doi-asserted-by": "crossref", "first-page": "252", "journal-title": "Adv Integr Med", "key": "2021031909151460000_8.1.e001568.42", "volume": "7", "year": "2020" }, { "DOI": "10.1136/bmjnph-2020-000095", "article-title": "Zinc as nutritional intervention and prevention measure for COVID-19 disease", "author": "Mossink", "doi-asserted-by": "crossref", "first-page": "111", "journal-title": "BMJ Nutr Prev Health", "key": "2021031909151460000_8.1.e001568.43", "volume": "3", "year": "2020" }, { "DOI": "10.1093/ajcn/85.3.837", "doi-asserted-by": "publisher", "key": "2021031909151460000_8.1.e001568.44" }, { "DOI": "10.1016/j.clnesp.2020.06.003", "article-title": "The key role of zinc in elderly immunity: a possible approach in the COVID-19 crisis", "author": "de Almeida Brasiel", "doi-asserted-by": "crossref", "first-page": "65", "journal-title": "Clin Nutr ESPEN", "key": "2021031909151460000_8.1.e001568.45", "volume": "38", "year": "2020" }, { "DOI": "10.1016/j.celrep.2019.07.085", "article-title": "MAVS O-GlcNAcylation is essential for host antiviral immunity against lethal RNA viruses", "author": "Song", "doi-asserted-by": "crossref", "first-page": "2386", "journal-title": "Cell Rep", "key": "2021031909151460000_8.1.e001568.46", "volume": "28", "year": "2019" }, { "DOI": "10.1016/j.imlet.2020.09.008", "article-title": "Azithromycin and glucosamine may amplify the type 1 interferon response to RNA viruses in a complementary fashion", "author": "DiNicolantonio", "doi-asserted-by": "crossref", "first-page": "83", "journal-title": "Immunol Lett", "key": "2021031909151460000_8.1.e001568.47", "volume": "228", "year": "2020" }, { "DOI": "10.1016/j.mehy.2020.109800", "article-title": "Targeting casein kinase 2 with quercetin or enzymatically modified isoquercitrin as a strategy for boosting the type 1 interferon response to viruses and promoting cardiovascular health", "author": "DiNicolantonio", "doi-asserted-by": "crossref", "journal-title": "Med Hypotheses", "key": "2021031909151460000_8.1.e001568.48", "volume": "142", "year": "2020" }, { "DOI": "10.1016/j.aimed.2020.07.007", "article-title": "The effect of quercetin on the prevention or treatment of COVID-19 and other respiratory tract infections in humans: a rapid review", "author": "Aucoin", "doi-asserted-by": "crossref", "first-page": "247", "journal-title": "Adv Integr Med", "key": "2021031909151460000_8.1.e001568.49", "volume": "7", "year": "2020" }, { "DOI": "10.32794/mr11250063", "article-title": "Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 pro): a case series", "author": "Castillo", "doi-asserted-by": "crossref", "first-page": "297", "journal-title": "Melatonin Res.", "key": "2021031909151460000_8.1.e001568.50", "volume": "3", "year": "2020" } ], "reference-count": 50, "references-count": 50, "relation": {}, "resource": { "primary": { "URL": "https://openheart.bmj.com/lookup/doi/10.1136/openhrt-2020-001568" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1136/crossmarkpolicy", "volume": "8" }