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

• Main Authors: Aleksandra Lange, Harry Huntress, Jesse Steindl, Przemyslaw Palka
• Format: Article
• Language: English
• Published: BMJ Publishing Group 2021-06-01
• Series: Open Heart
• Online Access: https://openheart.bmj.com/content/8/1/e001568.full

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.