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We review the melatonergic pathway role in viral infections, emphasizing influenza and covid\u201019 infections. Viral, or preexistent, suppression of pineal melatonin disinhibits neutrophil attraction, thereby contributing to an initial \u201ccytokine storm\u201d, as well as the regulation of other immune cells. Melatonin induces the circadian gene, Bmal1, which disinhibits the pyruvate dehydrogenase complex (PDC), countering viral inhibition of Bmal1\/PDC. PDC drives mitochondrial conversion of pyruvate to acetyl\u2010coenzyme A (acetyl\u2010CoA), thereby increasing the tricarboxylic acid cycle, oxidative phosphorylation, and ATP production. Pineal melatonin suppression attenuates this, preventing the circadian \u201cresetting\u201d of mitochondrial metabolism. This is especially relevant in immune cells, where shifting metabolism from glycolytic to oxidative phosphorylation, switches cells from reactive to quiescent phenotypes. Acetyl\u2010CoA is a necessary cosubstrate for arylalkylamine N\u2010acetyltransferase, providing an acetyl group to serotonin, and thereby initiating the melatonergic pathway. Consequently, pineal melatonin regulates mitochondrial melatonin and immune cell phenotype. Virus\u2010 and cytokine\u2010storm\u2010driven control of the pineal and mitochondrial melatonergic pathway therefore regulates immune responses. Virus\u2010and cytokine storm\u2010driven changes also increase gut permeability and dysbiosis, thereby suppressing levels of the short\u2010chain fatty acid, butyrate, and increasing circulating lipopolysaccharide (LPS). The alterations in butyrate and LPS can promote viral replication and host symptom severity via impacts on the melatonergic pathway. Focussing on immune regulators has treatment implications for covid\u201019 and other viral infections.<\/jats:p>","DOI":"10.1002\/rmv.2109","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T07:55:36Z","timestamp":1587455736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":173,"title":["Melatonin: Roles in influenza, Covid\u201019, and other viral infections"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7243-0817","authenticated-orcid":false,"given":"George","family":"Anderson","sequence":"first","affiliation":[{"name":"CRC Scotland &amp; London  London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russel J.","family":"Reiter","sequence":"additional","affiliation":[{"name":"Department of Cellular and Structural Biology University of Texas Health Science at San Antonio  San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.146"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.32794\/mr11250052"},{"key":"e_1_2_7_4_1","unstructured":"ZhouY HouY ShenJet al. 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