Conv. Plasma
Nigella Sativa

All melatonin studies
Meta analysis
study COVID-19 treatment researchMelatoninMelatonin (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Deficient synthesis of melatonin in COVID-19 can impair the resistance of coronavirus patients to mucormycosis

Sen, A., OSF Preprints, doi:0.31219/
Jul 2021  
  Source   PDF   All Studies   Meta AnalysisMeta
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.
Proposal that melatonin deficiency plays a significant role in COVID-19 associated mucormycosis.
Sen et al., 2 Jul 2021, preprint, 1 author.
This PaperMelatoninAll
Deficient synthesis of melatonin in COVID-19 can impair the resistance of coronavirus patients to mucormycosis
Amarnath Sen
Though it is thought that uncontrolled diabetes and the excessive use of corticosteroids are responsible for COVID-19 associated mucormycosis (CAM), researchers are on the lookout for additional reasons to explain the recent spurt of CAM in India. In the present paper it is argued that melatonin deficiency in COVID-19 plays a major role in CAM. Incidentally, melatonin is synthesized from tryptophan via the serotonin pathway and melatonin deficiency in COVID-19 arises from the faulty absorption of tryptophan from the food because SARS-COV-2 downregulates angiotensin-converting enzyme-2, which is the chaperone of the transporter of tryptophan, a key component in the process of uptake of tryptophan. The melatonin deficiency enhances the fungal virulence by facilitating iron acquisition and by promoting morphological transition of the mucor species from the yeast to the virulent hyphal form. Additionally, melatonin deficiency aggravates the suppression of T-cell immunity in the patients receiving steroids. Hence, the restoration of melatonin level should resolve the issues and help in defeating CAM, given the fact that melatonin is an iron chelator, inhibitor of myeloperoxidase, inhibitor of ferroptosis and pyroptosis and calmodulin blocker. Also, by lowering the expression of glucose-regulated protein-78, melatonin can further increase the resistance of diabetic patients to mucormycosis. Hence, clinical trials should be carried out to ascertain how tryptophan supplementation, administration of selective serotonin reuptake inhibitors (to increase serotonin, the precursor of melatonin), and exogenous melatonin help in correcting the melatonin deficiency and eliminating or reducing the propensity of the patients to CAM.
Almeida, Wilson, Hube, Candida albicans iron acquisition within the host, Yeast research
Aouichat, Navarro-Alarcon, Alarcón-Guijo, Salagre, Ncir et al., Melatonin Improves Endoplasmic Reticulum Stress-Mediated IRE1α Pathway in Zücker Diabetic Fatty Rat, Pharmaceuticals
Arastehfar, Carvalho A A R, Nguyen, Hedayati, Netea et al., COVID-19-Associated Candidiasis (CAC): An Underestimated Complication in the Absence of Immunological Predispositions?, J. Fungi
Arastehfar, Carvalho, Veerdonk, Jenks, Koehler et al., COVID-19 Associated Pulmonary Aspergillosis (CAPA)-From Immunology to Treatment, J. Fungi
Artis, Fountain, Delcher, Jones, A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability, Diabetes
Baltaci, Mogulkoc, Pinealectomy and melatonin administration in rats: their effects on plasma leptin levels and relationship with zinc, Acta Biol Hung
Benítez-King, Ríos, Martínez, Antón-Tay, In vitro inhibition of Ca2+/calmodulin-dependent kinase II activity by melatonin, Biochim. Biophys. Acta
Bro¨er, The Role of the Neutral Amino acid Transporter B 0 AT1 (SLC6A19) in Hartnup Disorder and Protein Nutrition, IUBMB Life
Castellano-Gonzalez, Clancy, Gottlieb, Prospects for adoptive T-cell therapy for invasive fungal disease, Curr Opin Infect Dis
Chand, Black fungus: More to it than just steroids
Do Amaral, Cipolla-Neto, A brief review about melatonin, a pineal hormone, Arch Endocrinol Metab
El-Missiry, El-Missiry, Othman, Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of Covid-19, European Journal of Pharmacology
Elkader, Aly, Protective effect of melatonin against iron overload-induced toxicity in rats, International Journal of Pharmacy and Pharmaceutical Sciences
Faramarzi, Sadighi, Chitsazi, Esmailzadeh, Foladvand, The effect of adjunctive use of melatonin as a supplement on serum ferritin level in periodontal patients: A randomized, controlled trial, Dental Research Journal
Favero, Franceschetti, Bonomini, Rodella, Rezzani, Melatonin as an Anti-Inflammatory Agent Modulating Inflammasome Activation, International Journal of Endocrinology
Ferreira, Soares, De Azevedo-Quintanilha, Da Silva-Gomes-Dias, Fintelman-Rodrigues et al., SARS-CoV-2 engages inflammasome and pyroptosis in human primary monocytes, Cell Death Discovery
Gou, Su, Hu, Zhou, Huang et al., Melatonin improves hypoxic-ischemic brain damage through the Akt/Nrf2/Gpx4 signaling pathway, Brain Research Bulletin
Gulcin, Buyukokuroglu, Kufrevioglu, Metal chelating and hydrogen peroxide scavenging effects of melatonin, J Pineal Res
Gupta, Haldar, Physiological crosstalk between melatonin and glucocorticoid receptor modulates T-cell mediated immune responses in a wild tropical rodent, Funambulus pennanti, J Steroid Biochem Mol Biol
Habib, Zaim, Ibrahim, The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators, Biomedicine & Pharmacotherapy
Hardeland, Melatonin -More than Just a Pineal Hormone, Biomed J Sci &Tech Res
Ibrahim, Spellberg, Edwards, Iron Acquisition: A Novel Prospective on Mucormycosis Pathogenesis and Treatment, Curr Opin Infect Dis
Ibrahim, Spellberg, Walsh, Kontoyiannis, Pathogenesis of Mucormycosis, Clinical Infectious Diseases
Jain, Over 21% black fungus patients non-Covid
John, Jacob, Kontoyiannis, When uncontrolled diabetes mellitus and severe COVID-19 converge: the perfect storm for mucormycosis, J Fungi
Jothimani, Kailasam, Danielraj, Nallathambi, Ramachandran et al., COVID-19: Poor outcomes in patients with zinc deficiency, Int J Infect Dis
Kernan, Carcillo, Hyperferritinemia and inflammation, International Immunology
Kumar, Black Fungus Cases Grow 150% In 3 Weeks To, Deaths Over
Labonia, Rubio, Arias, Melatonin corrects reticuloendothelial blockade and iron status in haemodialysed patients, Nephrology (Carlton)
Lee, Li, Calo, Heitman, Calcineurin Plays Key Roles in the Dimorphic Transition and Virulence of the Human Pathogenic Zygomycete Mucor circinelloides, PLoS Pathog
Li, Cao, Yin, -L, Huang et al., Ferroptosis: past, present and future, Cell Death and Disease
Park, Lee, Cardenas, Heitman, Calcium-calmodulin-calcineurin signaling: A globally conserved virulence cascade in eukaryotic microbial pathogens, Cell Host Microbe
Petrikkos, Tsioutis, Recent Advances in the Pathogenesis of mucormycoses, Clinical Therapeutics
Reynolds, Dubocovich, Melatonin multifaceted pharmacological actions on melatonin receptors converging to abrogate COVID-19, J Pineal Res
Ruscitti, Berardicurti, Benedetto, Cipriani, Iagnocco et al., Severe COVID-19, Another Piece in the Puzzle of the Hyperferritinemic Syndrome. An Immunomodulatory Perspective to Alleviate the Storm, Frontiers in Immunology
Savage, Zafar, Yohannan, Miller, Melatonin -StatPearls -NCBI Bookshelf
Sen, Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?, Med. Hypotheses
Shaeib, Khan, Ali, Najafi, Maitra et al., Melatonin Prevents Myeloperoxidase Heme Destruction and the Generation of Free Iron Mediated by Self-Generated Hypochlorous Acid, PLoS ONE
Shweta, Supriya, Laxminarayana, Vineeth, COVID-19 triggering mucormycosis in a susceptible patient: a new phenomenon in the developing world?, BMJ Case Rep
Singh, Singh, Joshi S R, Misra, Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India, Diabetes & Metabolic Syndrome, doi:10.1016/j.dsx.2021.05.0191871-4021/©2021
Skiada, Pavleas, Drogari-Apiranthitou, Epidemiology and diagnosis of mucormycosis: an update, J Fungi
Slominski, Hardeland, Zmijewski, Slominski, Reiter et al., Melatonin: A Cutaneous Perspective on its Production, Metabolism, and Functions, Journal of Investigative Dermatology
Stanford, Voigt, Iron Assimilation during Emerging Infections Caused by Opportunistic Fungi with emphasis on Mucorales and the Development of Antifungal Resistance, Genes
Symeonidis, The role of iron and iron chelators in zygomycosis, Clinical Microbiology and Infection
Tordjman, Chokron, Delorme, Charrier, Bellissant et al., Melatonin: Pharmacology, Functions and Therapeutic Benefits, Current Neuropharmacology
Yang, Lai, SARS-CoV-2 infection: can ferroptosis be a potential treatment target for multiple organ involvement? Cell Death Discovery
Zhou, Hou, Shen, Kallianpur, Zein et al., A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19, PLoS Biol
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop