Multiple actions of melatonin in reducing viral pathophysiologies

Melatonin and viral pathophysiology

  • Leonor Chacin-Bonilla Instituto de Investigaciones Clinicas, Universidad del Zulia, Apartado Postal 23, Maracaibo 4001-A, Venezuela
  • Ernesto Bonilla Instituto de Investigaciones Clinicas, Universidad del Zulia, Apartado Postal 23, Maracaibo 4001-A, Venezuela
Keywords: Melatonin, viral infections, immune, circadian, sirtuin, microbiome, SARS-CoV-2, treatment

Abstract

Viral infections lead to significant morbidity and mortality while the effective therapeutic approaches are lacking. Melatonin (MEL) (N-acetyl-5-methoxytryptamine) is a pleiotropic molecule that has a variety of functions, including the antiviral properties. It is a potent antioxidant, anti-inflammatory agent, a stimulator of immune functions, and regulator of apoptosis. These effects support the use of MEL in viral infections, which are often associated with excessive inflammatory responses and elevated oxidative stress. The virus- and cytokine- storm-driven control of the pineal and mitochondrial melatonergic pathway regulates immune responses and increases gut dysbiosis, suppressing levels of the short-chain fatty acid, butyrate, and increasing circulating lipopolysaccharides, stimulating viral replication and host symptoms severity. MEL has a contrasting role in controlling the pathophysiological effects of various viruses due to its chronobiotic, antioxidant and anti-inflammatory actions. Several recent preclinical and clinical studies have documented a robust protective effect of MEL against viral infections, including COVID-19 and it has emerged as an excellent candidate for protection against an array of different viruses. This review summarizes available data on the beneficial effects of MEL on viral pathophysiological actions, and also discusses and highlights likely evidence-based therapeutic applications.


 



References

1. Hosseinzadeh A, Kamrava SK, Joghataei MT, Darabi R, Shakeri-Zadeh A, Shahriari M, Reiter RJ, Ghaznavi H, Mehrzadi S (2016) Apoptosis signaling pathways in osteoarthritis and possible protective role of melatonin. J. Pineal Res. 61 (4): 411-425. doi: 10.1111/jpi.12362.
2. Reiter RJ (1991) Melatonin: That ubiquitously acting pineal hormone. Physiology 6 (5): 223-227. doi: 10.1152/physiologyonline.1991.6.5.223.
3. Valero N, Bonilla E, Pons H, Chacin-Bonilla L, Añez F, Espina LM, Medina-Leendertz S, García Tamayo J (2002) Melatonin induces changes to serum cytokines in mice infected with the Venezuelan equine encephalomyelitis virus. Trans. R. Soc. Trop. Med. Hyg. 96 (3): 348-351. doi: 10.1016/s0035-9203(02)90121-5.
4. Arias J, Meleán E, Valero N, Pons H, Chacín-Bonilla L, Larreal Y, Bonilla E (2003) Efecto de la melatonina en la proliferación linfocitaria y la producción de interleucina 2 (IL-2) e interleucina 1 beta (IL-1β) en esplenocitos de ratones. Invest. Clín. 44 (1): 41-50.
5. Bonilla E, Valero N, Chacín-Bonilla L, Pons H, Larreal Y, Medina-Leendertz S, Espina LM (2003) Melatonin increases interleukin-1β and decreases tumor necrosis factor alpha in the brain of mice infected with the Venezuelan equine encephalomyelitis virus. Neurochem. Res. 28 (5): 681-686. doi: 10.1023/a:1022897314108.
6. Valero N, Meleán E, Bonilla E, Arias J, Espina LM, Chacín-Bonilla L, Larreal Y, Maldonado M, Anez F (2005) In vitro, melatonin treatment decreases nitric oxide levels in murine splenocytes cultured with the Venezuelan equine encephalomyelitis virus. Neurochem. Res. 30 (11): 1439-1442. doi: 10.1007/s11064-005-8634-1.
7. Jou MJ, Peng TI, Yu PZ, Jou SB, Reiter RJ, Chen JY, Wu HY, Chen CC, Hsu LF (2007) Melatonin protects against common deletion of mitochondrial DNA-augmented mitochondrial oxidative stress and apoptosis. J. Pineal Res. 43 (4): 389-403. doi: 10.1111/j.1600-079X.2007.00490.x.
8. Hardeland R, Poeggeler B (2008) Melatonin beyond its classical functions. Open Physiol. J. 1: 1-23.
9. Hardeland R, Coto-Montes A (2010) New vistas on oxidative damage and aging. Open Biol. J. 3: 39-52. doi: 10.2174/18741967010030100039.
10. Mehrzadi S, Kamrava SK, Dormanesh B, Motevalian M, Hosseinzadeh A, Hosseini Tabatabaei SM, Ghaznavi H (2016) Melatonin synergistically enhances protective effect of atorvastatin against gentamicin-induced nephrotoxicity in rat kidney. Can. J. Physiol. Pharmacol. 94 (3): 265-271. doi: 10.1139/cjpp-2015-0277.
11. Jou MJ, Peng TI, Hsu LF, Jou SB, Reiter RJ, Yang CM, Chiao CC, Lin YF, Chen CC (2010) Visualization of melatonin's multiple mitochondrial levels of protection against mitochondrial Ca(2+)-mediated permeability transition and beyond in rat brain astrocytes. J. Pineal Res. 48 (1): 20-38. doi: 10.1111/j.1600-079X.2009.00721.x.
12. Acuña Castroviejo D, López LC, Escames G, López A, García JA, Reiter RJ (2011) Melatonin-mitochondria interplay in health and disease. Curr. Top. Med. Chem. 11 (2): 221-240. doi: 10.2174/156802611794863517.
13. Rodella LF, Filippini F, Bonomini F, Bresciani R, Reiter RJ, Rezzani R (2010) Beneficial effects of melatonin on nicotine-induced vasculopathy. J. Pineal Res. 48 (2): 126-132. doi: 10.1111/j.1600-079X.2009.00735.x.
14. de Castro-Silva C, de Bruin VM, Cunha GM, Nunes DM, Medeiros CA, de Bruin PF (2010) Melatonin improves sleep and reduces nitrite in the exhaled breath condensate in cystic fibrosis-a randomized, double-blind placebo-controlled study. J. Pineal Res. 48 (1): 65-71. doi: 10.1111/j.1600-079X.2009.00726.x.
15. Park SY, Jang WJ, Yi EY, Jang JY, Jung Y, Jeong JW, Kim YJ (2010) Melatonin suppresses tumor angiogenesis by inhibiting HIF-1alpha stabilization under hypoxia. J. Pineal Res. 48 (2): 178-184. doi: 10.1111/j.1600-079x.2009.00742.x.
16. Bonnefont-Rousselot D, Collin F (2010) Melatonin: action as antioxidant and potential applications in human disease and aging. Toxicology 278 (1): 55-67. doi: 10.1016/j.tox.2010.04.008.
17. Gitto E, Aversa S, Reiter RJ, Barberi I, Pellegrino S (2011) Update on the use of melatonin in pediatrics. J. Pineal Res. 50 (1): 21-28. doi: 10.1111/j.1600-079X.2010.00814.x.
18. Chen CF, Wang D, Reiter RJ, Yeh DY (2011) Oral melatonin attenuates lung inflammation and airway hyperreactivity induced by inhalation of aerosolized pancreatic fluid in rats. J. Pineal Res. 50 (1): 46-53. doi:10.1111/j.1600-079X.2010.00808.x
19. Sánchez-Barceló EJ, Mediavilla MD, Tan DX, Reiter RJ (2010) Clinical uses of melatonin: evaluation of human trials. Curr. Med. Chem. 17 (19): 2070-2095. doi: 10.2174/092986710791233689.
20. Reiter RJ, Tan DX, Sainz RM, Mayo JC, Lopez-Burillo S (2002) Melatonin: reducing the toxicity and increasing the efficacy of drugs. J. Pharm. Pharmacol. 54 (10): 1299-1321. doi: 10.1211/002235702760345374.
21. Reiter RJ, Sharma R, Tan DX, Huang G, de Almeida Chuffa LG, Anderson G (2023) Melatonin modulates tumor metabolism and mitigates metastasis. Expert Rev. Endocrinol. Metab. 18 (4): 321-336. doi: 10.1080/17446651.2023.223 7103.
22. Andersen LP, Gögenur I, Rosenberg J, Reiter RJ (2016). The safety of melatonin in humans. Clin. Drug Investig. 36 (3): 169-175. doi: 10.1007/s40261-015-0368-5.
23. Vielma JR, Bonilla E, Chacín-Bonilla L, Mora M, Medina-Leendertz S, Bravo Y (2014) Effects of melatonin on oxidative stress, and resistance to bacterial, parasitic, and viral infections: A review. Acta Trop. 137: 31-38. doi: 10.1016/j.actatropica.2014.04.021.
24. Chacín-Bonilla L, Vielma JR, Bonilla E (2014) Should melatonin be considered a complementary or alternative therapy against parasitic infections? Epidemiol. 4: e117. doi: 10.4172/2161-1165.1000e117.
25. Cárdenas R, Chacín-Bonilla L, Bonilla E (2023) Melatonin: A review of its physiopathological and therapeutic relationship with parasitic diseases. Melatonin Res. 6 (1): 28-50. doi: 10.32794/mr112500139.
26. Boga JA, Coto-Montes A, Rosales-Corral SA, Tan DX, Reiter RJ (2012). Beneficial actions of melatonin in the management of viral infections: a new use for this "molecular handyman"? Rev. Med. Virol. 22 (5): 323-338. doi: 10.100 2/rmv.1714.
27. Juybari KB, Pourhanifeh MH, Hosseinzadeh A, Hemati K, Mehrzadi S (2020) Melatonin potentials against viral infections including COVID-19: Current evidence and new findings. Virus Res. 287: 198108. doi: 10.1016%2Fj.virus res.2020.198108.
28. Alomari T, Al-Abdallat H, Hamamreh R, Alomari O, Hos BH, Reiter RJ (2023). Assessing the antiviral potential of melatonin: A comprehensive systematic review. Rev. Med. Virol. 21: e2499. doi: 10.1002/rmv.2499.
29. Anderson G, Reiter RJ (2020) Melatonin: Roles in influenza, Covid-19, and other viral infections. Rev. Med. Virol. 30 (3): e2109. doi: 10.1002/rmv.2109.
30. Reiter RJ, Ma Q, Sharma R (2020) Treatment of Ebola and other infectious diseases: Melatonin “goes viral”. Melatonin Res. 3 (1): 43-57. doi: 10.32794/mr112500 47.
31. Chacín-Bonilla L, Bonilla E (2023) Melatonin and Covid-19: An opened Pandora’s box and the hope for the time being. Melatonin Res. 6 (4): 474-484. doi: 10.32794/mr1125 00163.
32. Hernández-Ruiz J, Giraldo-Acosta M, El Mihyaoui A, Cano A, Arnao MB (2023) Melatonin as a possible natural anti-viral compound in plant biocontrol. Plants (Basel) 12 (4): 781. doi: 10.3390/plants12040781.
33. Maestroni GJ, Conti A, Pierpaoli W (1988) Pineal melatonin, its fundamental immunoregulatory role in aging and cancer. Ann. N. Y. Acad. Sci. 521: 140-148. doi: 10.1111/j.1749-6632.1988.tb35272.x.
34. Ben-Nathan D, Maestroni GJ, Lustig S, Conti A (1995) Protective effects of melatonin in mice infected with encephalitis viruses. Arch. Virol. 140 (2): 223-230. doi: 10.1007/BF01309858.
35. Tan DX, Korkmaz A, Reiter RJ, Manchester LC (2014) Ebola virus disease: potential use of melatonin as a treatment. J. Pineal Res. 57 (4): 381-384. doi: 10.1111/jpi.12186.
36. Wongchitrat P, Montri Yasawong M, and Watthanachai Jumpathong W, Tipsuda Chanmanee T, Samutpong A, Dangsakul W, Govitrapong P, Reiter RJ, Puthavathana P (2022) Melatonin inhibits Zika virus replication in Vero epithelial cells and SK-N-SH human neuroblastoma cells. Melatonin Res. 5 (2): 171-185. doi: 10.32794/mr112500127.
37. Reiter RJ, Sharma R, Simko F, Dominguez-Rodriguez A, Tesarik J, Neel RL, Slominski AT, Kleszczynski K, Martin-Gimenez VM, Manucha W, Cardinali DP (2022) Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection. Cell Mol. Life Sci. 79 (3): 143. doi: 10.1007/s00018-021-04102-3.
38. Loh D, Reiter RJ (2022). Melatonin: Regulation of viral phase separation and Epitranscriptomics in post-acute sequelae of COVID-19. Int. J. Mol. Sci. 23 (15): 8122. doi: 10.3390/ijms23158122.
39. Lan SH, Lee HZ, Chao CM, Chang SP, Lu LC, Lai CC (2022) Efficacy of melatonin in the treatment of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials. J. Med. Virol. 94 (5): 2102-2107. doi: 10.1002/jmv.27595.
40. Molina-Carballo A, Jerez-Calero AE, Fernández-López L, Augustin-Morales MC, Muñoz-Hoyos A, Agil A (2023). The preventive and protective role of melatonin in SARS-CoV-2 infection: a retrospective study. Melatonin Res. 6 (3): 372-396. doi:10.32794/mr11250015912500159.
41. Zhang R, Wang X, Ni L, Di X, Ma B, Niu S, Liu C, Reiter RJ (2020) COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 250: 117583. doi: 10.1016/j.1fs. 2020.117583.
42. Ryu WS (2017) Virus life cycle. Molecular virology of human pathogenic viruses. In Molecular virology of human pathogenic viruses, eds Ryu WS (Academic Press, Boston), pp 31-45.
43. Zhuang X, Forde D, Tsukuda S, D'Arienzo V, Mailly L, Harris JM, Wing PAC, Borrmann H, Schilling M, Magri A, Rubio CO, Maidstone RJ, Iqbal M, Garzon M, Minisini R, Pirisi M, Butterworth S, Balfe P, Ray DW, Watashi K, Baumert TF, McKeating JA (2021) Circadian control of hepatitis B virus replication. Nat. Commun. 12 (1): 1658. doi: 10.1038/s41467-021-21821-0.
44. Scheiermann C, Gibbs J, Ince L, Loudon A (2018) Clocking in to immunity. Nat. Rev. Immunol. 18 (7): 423-437. doi: 10.1038/s41577-018-0008-4.
45. Tan D-X, Chen LD, Poeggeler B, Manchester LC, Reiter RJ (1993) Melatonin: a potent, endogenous hydroxyl radical scavenger. Endocr. J. 1: 57-60.
46. Reiter RJ, Tan DX, Manchester LC, Qi W (2001) Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell. Biochem. Biophys. 34 (2): 237-256. doi: 10.1385/CBB:34:2:237.26.
47. Guerrero JM, Reiter RJ (2002) Melatonin-immune system relationships. Curr. Top. Med. Chem. 2 (2): 167-179. doi: 10.2174/1568026023394335.
48. Mayo JC, Sainz RM, González-Menéndez P, Hevia D, Cernuda-Cernuda R (2017) Melatonin transport into mitochondria. Cell Mol. Life Sci. 74 (21): 3927-3940. doi: 10.1007/s00018-017-2616-8.
49. Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, Ostrom RS, Slominski AT (2012) Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol. Cell Endocrinol. 351 (2): 152-166. doi: 10.1016/j.mce.2012. 01.004.
50. Boutin JA (2016) Quinone reductase 2 as a promising target of melatonin therapeutic actions. Expert Opin. Ther. Targets 20 (3): 303-317. doi: 10.1517/ 14728222.2016.109 1882.
51. Martín Giménez VM, de Las Heras N, Lahera V, Tresguerres JAF, Reiter RJ, Manucha W (2022) Melatonin as an anti-aging therapy for age-related cardiovascular and neurodegenerative diseases. Front. Aging Neurosci. 14: 888292. doi: 10.3389/fnagi.2022.888292.
52. Chacín-Bonilla L, Cardenas R, Bonilla E (2022) Melatonin: The continuing neuroprotective promise of a versatile molecule. Int. J. Case Rep. 8 (1): 9-12. doi: 10.37871/ijcrsr.id99.
53. Panmak P, Nopparat C, Permpoonpattana K, Namyen J, Govitrapong P (2021) Melatonin protects against methamphetamine-induced Alzheimer's disease-like pathological changes in rat hippocampus. Neurochem. Int.148: 105121. doi: 10.1016/j.neuint.2021.105121.
54. Maestroni GJ (1999) Therapeutic potential of melatonin in immunodeficiency states, viral diseases, and cancer. Adv. Exp. Med. Biol. 467: 217-226. doi: 10.1007/978-1-4615-4709-9_28.
55. Huang SH, Cao XJ, Liu W, Shi XY, Wei W (2010) Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice. J. Pineal Res. 48 (2): 109-16. doi: 10.1111/j.1600-079X.2009.00733.x.
56. Hardeland R (2018) Melatonin and inflammation-story of a double-edged blade. J. Pineal Res. 65 (4): e12525. doi: 10.1111/jpi.12525.
57. Bazyar H, Gholinezhad H, Moradi L, Salehi P, Abadi F, Ravanbakhsh M, Zare Javid A (2019) The effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 diabetes mellitus patients with chronic periodontitis: A double-blind, placebo-controlled trial. Inflammopharmacology 27 (1): 67-76. doi: 10.1007/s10787-018-0539-0.
58. Sánchez-López AL, Ortiz GG, Pacheco-Moises FP, Mireles-Ramírez MA, Bitzer-Quintero OK, Delgado-Lara DLC, Ramírez-Jirano LJ, Velázquez-Brizuela IE (2018) Efficacy of melatonin on serum pro-inflammatory cytokines and oxidative stress markers in relapsing remitting multiple sclerosis. Arch. Med. Res. 49 (6): 391-398. doi:10.1016/ j.arcmed.2018.12.004.
59. Kücükakin B, Lykkesfeldt J, Nielsen HJ, Reiter RJ, Rosenberg J, Gögenur I (2008) Utility of melatonin to treat surgical stress after major vascular surgery-a safety study. J. Pineal Res. 44 (4): 426-431. doi: 10.1111/j.1600-079X.2007.00545.x.
60. Zhao Z, Lu C, Li T, Wang W, Ye W, Zeng R, Ni L, Lai Z, Wang X, Liu C (2018). The protective effect of melatonin on brain ischemia and reperfusion in rats and humans: In vivo assessment and a randomized controlled trial. J. Pineal Res. 65 (4): e12521. doi: 10.1111/jpi.12521.
61. Cheng J, Yang HL, Gu CJ, Liu YK, Shao J, Zhu R, He YY, Zhu XY, Li MQ (2019) Melatonin restricts the viability and angiogenesis of vascular endothelial cells by suppressing HIF- 1α/ROS/VEGF. Int. J. Mol. Med. 43 (2): 945-955. doi:10.3892/ijmm. 2018.4021.
62. Brennan K, Bowie AG (2010) Activation of host pattern recognition receptors by viruses. Curr. Opin. Microbiol. 13 (4): 503-507. doi: 10.1016/j.mib.2010.05.007.
63. Loo YM, Gale M Jr (2011) Immune signaling by RIG-I-like receptors. Immunity 34 (5): 680-692. doi: 10.1016/j.immuni.2011.05.003.
64. Fensterl V, Sen GC (2009) Interferons and viral infections. Biofactors 35 (1): 14-20. doi: 10.1002/biof.6.
65. Malmgaard L (2004) Induction and regulation of IFNs during viral infections. J. Interferon Cytokine Res. 24 (8): 439-454. doi: 10.1089/1079990041689665.
66. Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 7: 145-173. doi: 10.1146/annurev.iy.07.040189.001045.
67. Carrillo-Vico A, Reiter RJ, Lardone PJ, Herrera JL, Fernández-Montesinos R, Guerrero JM, Pozo D (2006) The modulatory role of melatonin on immune responsiveness. Curr. Opin. Investig. Drugs 7 (5): 423-431.
68. Radogna F, Diederich M, Ghibelli L (2010) Melatonin: a pleiotropic molecule regulating inflammation. Biochem. Pharmacol. 80 (12): 1844-1852. doi: 10.1016/ j.bcp.2010.07.041.
69. Morrey KM, McLachlan JA, Serkin CD, Bakouche O (1994) Activation of human monocytes by the pineal hormone melatonin. J. Immunol. 153 (6): 2671-2680.
70. Garcia-Mauriño S, Gonzalez-Haba MG, Calvo JR, Rafii-El-Idrissi M, Sanchez-Margalet V, Goberna R, Guerrero JM (1997) Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4+ cells: a possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes. J. Immunol. 159 (2): 574-581.
71. Finocchiaro LM, Arzt ES, Fernández-Castelo S, Criscuolo M, Finkielman S, Nahmod VE (1988) Serotonin and melatonin synthesis in peripheral blood mononuclear cells: stimulation by interferon-gamma as part of an immunomodulatory pathway. J. Interferon Res. 8 (6): 705-716. doi: 10.1089/ jir.1988.8.705.
72. Markus RP, Sousa KS, da Silveira Cruz-Machado S, Fernandes PA, Ferreira ZS (2021) Possible role of pineal and extra-pineal melatonin in surveillance, immunity, and first-line defense. Int. J. Mol. Sci. 22 (22): 12143. doi: 10.3390/ijms222212143.
73. Bonilla E, Valero N, Chacín-Bonilla L, Medina-Leendertz S (2004) Melatonin and viral infections. J. Pineal Res. 36 (2): 73-79. doi: 10.1046/j.1600-079x.2003.00105.x.
74. Currier NL, Sun LZ, Miller SC (2000) Exogenous melatonin: quantitative enhancement in vivo of cells mediating non-specific immunity. J. Neuroimmunol. 104 (2): 101-108. doi: 10.1016/s0165-5728(99)00271-4.
75. Castrillón PO, Esquifino AI, Varas A, Zapata A, Cutrera RA, Cardinali DP (2000) Effect of melatonin treatment on 24-h variations in responses to mitogens and lymphocyte subset populations in rat submaxillary lymph nodes. J. Neuroendocrinol. 12 (8): 758-765. doi: 10.1046/j.1365-2826.2000.00519.x.
76. Li-Sha G, Jing-Lin Z, Li L, Guang-Yi C, Xiao-Wei L, Yue-Chun L (2016) Nicotine inhibits the production of proinflammatory cytokines of mice infected with coxsackievirus B3. Life Sci. 148: 9-16. doi: 10.1016/j.lfs.2016.02.003.
77. Cui WY, Zhao S, Polanowska-Grabowska R, Wang J, Wei J, Dash B, Chang SL, Saucerman JJ, Gu J, Li MD (2013) Identification and characterization of poly(I:C)-induced molecular responses attenuated by nicotine in mouse macrophages. Mol. Pharmacol. 83 (1): 61-72. doi: 10.1124/mol.112.081497.
78. Cardinali DP, Brown GM, Pandi-Perumal SR (2020) Can melatonin be a potential "silver bullet" in treating COVID-19 patients? Diseases 8 (4): 44. doi: 10.3390/ diseases8040044.
79. Moreno ACR, Porchia BFMM, Pagni RL, Souza PDC, Pegoraro R, Rodrigues KB, Barros TB, Aps LRMM, de Araújo EF, Calich VLG, Ferreira LCS (2018) The combined use of melatonin and an indoleamine 2,3-Dioxygenase-1 inhibitor enhances vaccine-induced protective cellular immunity to HPV16-associated tumors. Front. Immunol. 9: 1914. doi: 10.3389/fimmu.2018.01914.
80. Baghban Rahimi S, Mohebbi A, Vakilzadeh G, Biglari P, Razeghi Jahromi S, Mohebi SR, Shirian S, Gorji A, Ghaemi A (2018) Enhancement of therapeutic DNA vaccine potency by melatonin through inhibiting VEGF expression and induction of antitumor immunity mediated by CD8+ T cells. Arch. Virol. 163 (3): 587-597. doi: 10.1007/s00705-017-3647-z.
81. Negrette B, Bonilla E, Valero N, Pons H, Tamayo JG, Chacín-Bonilla L, Medina- Leendertz S, Añez F (2001) Melatonin treatment enhances the efficiency of mice immunization with Venezuelan equine encephalomyelitis virus TC-83. Neurochem. Res. 26 (7): 767-770. doi: 10.1023/a:1011645400123.
82. Regodón S, Martín-Palomino P, Fernández-Montesinos R, Herrera JL, Carrascosa-Salmoral MP, Píriz S, Vadillo S, Guerrero JM, Pozo D (2005) The use of melatonin as a vaccine agent. Vaccine 23 (46-47): 5321-5327. doi: 10.1016/j.vaccine.2005.07.003.
83. Reiter RJ, Mayo JC, Tan DX, Sainz RM, Alatorre-Jimenez M, Qin L (2016) Melatonin as an antioxidant: under promises but over delivers. J. Pineal Res. 61 (3): 253-278. doi: 10.1111/jpi.12360.
84. Galano A, Tan DX, Reiter RJ (2018) Melatonin: A versatile protector against oxidative DNA damage. Molecules 23 (3): 530. doi: 10.3390/molecules23030530
85. Tan DX, Manchester LC, Qin L, Reiter RJ (2016) Melatonin: A mitochondrial targeting molecule involving mitochondrial protection and dynamics. Int. J. Mol. Sci. 17 (12): 2124. doi: 10.3390/ijms17122124.
86. Hardeland R (2011) Melatonin and its metabolites as antinitrosating and antinitrating agents. J. Exp. Integr. Med. 1 (2): 67-81. doi: 10.5455/jeim.111210. ir.003.
87. Tomás-Zapico C, Coto-Montes A (2005) A proposed mechanism to explain the stimulatory effect of melatonin on antioxidative enzymes. J. Pineal Res. 39 (2): 99-104. doi: 10.1111/j.1600-079X.2005.00248.x.
88. Zhang HM, Zhang Y (2014) Melatonin: a well-documented antioxidant with conditional pro-oxidant actions. J. Pineal Res. 57 (2): 131-146. doi: 10.1111/jpi.
89. Reiter RJ, Tan DX, Fuentes-Broto L (2010) Melatonin: a multitasking molecule. Prog. Brain Res. 181:127-151. doi: 10.1016/S0079-6123(08)81008-4.
90. Cipolla-Neto J, Amaral FGD (2018) Melatonin as a hormone: New physiological and clinical insights. Endocr. Rev. 39 (6): 990-1028. doi: 10.1210/ er.2018-00084.
91. Hardeland R (2016) Melatonin in plants - diversity of levels and multiplicity of functions. Front. Plant Sci. 7: 198. doi: 10.3389/fpls.2016.00198.
92. Venegas C, García JA, Escames G, Ortiz F, López A, Doerrier C, García-Corzo L, López LC, Reiter RJ, Acuña-Castroviejo D (2012) Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations. J. Pineal Res. 52 (2): 217-227. doi: 10.1111/j.1600-079X.2011.00931.x.
93. Suofu Y, Li W, Jean-Alphonse FG, Jia J, Khattar NK, Li J, Baranov SV, Leronni D, Mihalik AC, He Y, Cecon E, Wehbi VL, Kim J, Heath BE, Baranova OV, Wang X, Gable MJ, Kretz ES, Di Benedetto G, Lezon TR, Ferrando LM, Larkin TM, Sullivan M, Yablonska S, Wang J, Minnigh MB, Guillaumet G, Suzenet F, Richardson RM, Poloyac SM, Stolz DB, Jockers R, Witt-Enderby PA, Carlisle DL, Vilardaga JP, Friedlander RM (2017) Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. Proc. Natl. Acad. Sci. 114 (38): E7997-E8006. doi: 10.1073/pnas.1705768114.
94. Reiter RJ, Sharma R, Rosales-Corral S, de Campos Zuccari DAP, de Almeida Chuffa LG (2022) Melatonin: A mitochondrial resident with a diverse skill set.
Life Sci. 301: 120612. doi: 10.1016/j.lfs.2022.120612.
95. Córdoba-Moreno MO, Santos GC, Muxel SM, Dos Santos-Silva D, Quiles CL, Sousa KDS, Markus RP, Fernandes PACM (2023) IL-10-induced STAT3/NF-κB crosstalk modulates pineal and extra-pineal melatonin synthesis. J. Pineal Res. 22: e12923. doi: 10.1111/jpi.12923.
96. Reiter RJ, Tan DX, Rosales-Corral S, Galano A, Jou MJ, Acuna-Castroviejo D (2018) Melatonin mitigates mitochondrial meltdown: Interactions with SIRT3. Int. J Mol. Sci. 19 (8): 2439. doi: 10.3390/ijms19082439.
97. Liu L, Cao Q, Gao W, Li B, Xia Z, Zhao B (2021) Melatonin protects against focal cerebral ischemia-reperfusion injury in diabetic mice by ameliorating mitochondrial impairments: involvement of the Akt-SIRT3-SOD2 signaling pathway. Aging (Albany, NY) 13 (12): 16105-16123. doi: 10.18632/aging.203137.
98. Reiter RJ, Ma Q, Sharma R (2020) Melatonin in mitochondria: Mitigating clear and present dangers. Physiology (Bethesda). 35 (2): 86-95. doi: 10.1152/ physiol.00034.2019.
99. Reiter RJ, Sharma R, Rosales-Corral S, Manucha W, Chuffa LGA, Zuccari DAPC (2021) Melatonin and pathological cell interactions: Mitochondrial glucose processing in cancer cells. Int. J. Mol. Sci. 22: 12494. doi: 10.3390/ijms2222 12494.
100. Park JW, Hwang MS, Suh SI, Baek WK (2009) Melatonin down-regulates HIF-1 alpha expression through inhibition of protein translation in prostate cancer cells. J. Pineal Res. 46 (4): 415-421. doi: 10.1111/j.1600-079X.2009.00678.x.
101. Mota A, Jardim-Perassi B, de Castro T, Colomb J., Sonehara N, Nishiyama V, Pierri V, Zuccari D (2019) Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer. Melatonin Res. 2 (4): 83-98. doi: 10.32794/mr11250042.
102. Glancy B, Kane DA, Kavazis AN, Goodwin ML, Willis WT, Gladden LB (2021) Mitochondrial lactate metabolism: history and implications for exercise and disease. J. Physiol. 599 (3): 863-888. doi: 10.1113/JP278930.
103. Warburg O (1956) On respiratory impairment in cancer cells. Science 124 (3215): 269-270.
104. Robey IF, Lien AD, Welsh SJ, Baggett BK, Gillies RJ (2005) Hypoxia-inducible factor-1alpha and the glycolytic phenotype in tumors. Neoplasia 7 (4): 324-330. doi: 10.1593/neo.04430.
105. Truong KK, Lam MT, Grandner MA, Sassoon CS, Malhotra A (2016) Timing matters: Circadian rhythm in sepsis, obstructive lung disease, obstructive sleep apnea, and cancer. Ann. Am. Thorac. Soc. 13 (7): 1144-1154. doi: 10.1513/AnnalsATS.201602-125FR.
106. Foteinou PT, Venkataraman A, Francey LJ, Anafi RC, Hogenesch JB, Doyle FJ 3rd (2018) Computational and experimental insights into the circadian effects of SIRT1. Proc. Natl. Acad. Sci. U S A. 115 (45): 11643-11648. doi: 10.1073/pnas.1803410115.
107. Tu Y, Song E, Wang Z, Ji N, Zhu L, Wang K, Sun H, Zhang Y, Zhu Q, Liu X, Zhu M (2021) Melatonin attenuates oxidative stress and inflammation of Müller cells in diabetic retinopathy via activating the Sirt1 pathway. Biomed. Pharmacother. 137: 111274. doi: 10.1016/j.biopha.2021.111274.
108. Koyuncu E, Budayeva HG, Miteva YV, Ricci DP, Silhavy TJ, Shenk T, Cristea IM (2014) Sirtuins are evolutionarily conserved viral restriction factors. mBio. 5 (6): e02249-14. doi: 10.1128/mBio.02249-14.
109. Markus RP, Silva CL, Franco DG, Barbosa EM Jr, Ferreira ZS (2010) Is modulation of nicotinic acetylcholine receptors by melatonin relevant for therapy with cholinergic drugs? Pharmacol. Ther. 126 (3): 251-262. doi: 10.1016/j.pharmthera.2010.02.009.
110. Zhao D, Yu Y, Shen Y, Liu Q, Zhao Z, Sharma R, Reiter RJ (2019) Melatonin synthesis and function: Evolutionary history in animals and plants. Front. Endocrinol. (Lausanne) 10: 249. doi: 10.3389/fendo.2019.00249.
111. Anderson G, Maes M (2017) Interactions of tryptophan and its catabolites with melatonin and the alpha 7 nicotinic receptor in central nervous system and psychiatric disorders: Role of the aryl hydrocarbon receptor and direct mitochondria regulation. Int. J. Tryptophan Res. 10: 1178646917691738. doi: 10.1177/1178646917691738.
112. Reiter RJ, Sharma R, Ma Q, Rosales-Corral SA, Acuna-Castroviejo D, Escames G (2019) Inhibition of mitochondrial pyruvate dehydrogenase kinase: A proposed mechanism by which melatonin causes cancer cells to overcome aerobic glycolysis, limit tumor growth and reverse insensitivity to chemotherapy. Melatonin Res. 2 (3): 105-119. doi: 10.32794/ mr11250033.
113. Danthi P (2011) Enter the kill zone: initiation of death signaling during virus entry. Virology 411: 316-324. doi: 10.1016/j.virol.2010.12.043.
114. Begum R, Mamun-Or-Rashid ANM, Lucy TT, Pramanik MK, Sil BK, Mukerjee N, Tagde P, Yagi M, Yonei Y (2022) Potential therapeutic approach of melatonin against Omicron and some other variants of SARS-CoV-2. Molecules 27 (20): 6934. doi: 10.3390/molecules27206934.
115. Suhy DA, Giddings TH Jr, Kirkegaard K (2000) Remodeling the endoplasmic reticulum by poliovirus infection and by individual viral proteins: an autophagy-like origin for virus-induced vesicles. J. Virol. 74 (19): 8953-8965. doi: 10.1128/jvi.74.19.8953-8965.2000.
116. Anelli T, Sitia R (2008) Protein quality control in the early secretory pathway. EMBO J. 27 (2): 315-327. doi: 10.1038/sj.emboj.7601974.
117. Tan D-X, Reiter RJ (2019) Mitochondria: the birth place, battle ground and the site of melatonin metabolism in cells. Melatonin Res. 2 (1): 44-66. doi: 10.32794/ mr11250011.
118. Grose C (2010) Autophagy during common bacterial and viral infections of children. Pediatr. Infect. Dis. J. 29 (11): 1040-1042. doi: 10.1097/INF.0b013e3 181e77f43.
119. Dreux M, Chisari FV (2009) Autophagy proteins promote hepatitis C virus replication. Autophagy 5 (8): 1224-1225. doi: 10.4161/auto.5.8.10219.
120. Vega-Naredo I, Caballero B, Sierra V, García-Macia M, de Gonzalo-Calvo D, Oliveira PJ, Rodríguez-Colunga MJ, Coto-Montes A (2012) Melatonin modulates autophagy through a redox-mediated action in female Syrian hamster Harderian gland controlling cell types and gland activity. J. Pineal Res. 52 (1): 80-92. doi: 10.1111/j.1600-079X.2011.00922.x.
121. Bonilla E, Valero N, Pons H, Chacín-Bonilla L (1997) Melatonin protects mice infected with Venezuelan equine encephalomyelitis virus. Cell Mol. Life Sci. 53 (5): 430-434. doi: 10.1007/s000180050051.
122. Morchang A, Malakar S, Poonudom K, Noisakran S, Yenchitsomanus PT, Limjindaporn T (2021) Melatonin inhibits dengue virus infection via the sirtuin 1-mediated interferon pathway. Viruses 13 (4): 659. doi: 10.3390/v13040659.
123. Hill-Batorski L, Halfmann P, Neumann G, Kawaoka Y (2013). The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication. J. Virol. 87 (24): 13795-802. doi: 10.1128/JVI.02422-13.
124. Kitidee K, Samutpong A, Pakpian N Wisitponchai T, Govitrapong P, Reiter RJ, Wongchitrat P (2023) Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells. Sci. Rep. 13: 6063. doi: 10.1038/s41598-023-33254-4.
125. Kalita E, Panda M, Prajapati VK (2023) The interplay between circadian clock and viral infections: A molecular perspective. Adv. Protein Chem. Struct. Biol. 137: 293-330. doi: 10.1016/bs.apcsb.2023.02.009.
126. Zhuang X, Tsukuda S, Wrensch F, Wing PAC, Schilling M, Harris JM, Borrmann H, Morgan SB, Cane JL, Mailly L, Thakur N, Conceicao C, Sanghani H, Heydmann L, Bach C, Ashton A, Walsh S, Tan TK, Schimanski L, Huang KA, Schuster C, Watashi K, Hinks TSC, Jagannath A, Vausdevan SR, Bailey D, Baumert TF, McKeating JA (2021) The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells. iScience 24 (10): 103144. doi: 10.1016/j.isci.2021.103144.
127. Edgar RS, Stangherlin A, Nagy AD, Nicoll MP, Efstathiou S, O'Neill JS, Reddy AB (2016) Cell autonomous regulation of herpes and influenza virus infection by the circadian clock. Proc. Natl. Acad. Sci. U S A. 113 (36): 10085-10090. doi: 10.1073/pnas.1601895113.
128. Sundar IK, Ahmad T, Yao H, Hwang JW, Gerloff J, Lawrence BP, Sellix MT, Rahman I (2015) Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD. Sci. Rep. 4: 9927. doi: 10.1038/srep09927.
129. Rosenberger CM, Podyminogin RL, Navarro G, Zhao GW, Askovich PS, Weiss MJ, Aderem A (2012) miR-451 regulates dendritic cell cytokine responses to influenza infection. J. Immunol. 189 (12): 5965-5975. doi: 10.4049/ jimmunol.1201437.
130. Buggele WA, Johnson KE, Horvath CM (2012) Influenza A virus infection of human respiratory cells induces primary microRNA expression. J. Biol. Chem. 287 (37): 31027-31040. doi: 10.1074/jbc.M112.387670.
131. Yang SL, Yu C, Jiang JX, Liu LP, Fang X, Wu C (2014) Hepatitis B virus X protein disrupts the balance of the expression of circadian rhythm genes in hepatocellular carcinoma. Oncol. Lett. 8 (6): 2715-2720. doi: 10.3892/ol.2014.2570.
132. Horii R, Honda M, Shirasaki T, Shimakami T, Shimizu R, Yamanaka S, Murai K, Kawaguchi K, Arai K, Yamashita T, Sakai Y, Yamashita T, Okada H, Nakamura M, Mizukoshi E, Kaneko S (2019) MicroRNA-10a impairs liver metabolism in hepatitis C virus-related cirrhosis through deregulation of the circadian clock gene brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1. Hepatol. Commun. 3 (12): 1687-1703. doi: 10.1002/hep4.1431.
133. Benegiamo G, Mazzoccoli G, Cappello F, Rappa F, Scibetta N, Oben J, Greco A, Williams R, Andriulli A, Vinciguerra M, Pazienza V (2013) Mutual antagonism between circadian protein period 2 and hepatitis C virus replication in hepatocytes. PLoS One. 8 (4): e60527. doi: 10.1371/journal.pone.0060527.
134. Duncan MJ, Bruce-Keller AJ, Conner C, Knapp PE, Xu R, Nath A, Hauser KF (2008) Effects of chronic expression of the HIV-induced protein, transactivator of transcription, on circadian activity rhythms in mice, with or without morphine. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295 (5): R1680-1687. doi: 10.1152/ajpregu.90496.2008.
135. Clark JP 3rd, Sampair CS, Kofuji P, Nath A, Ding JM (2005) HIV protein, transactivator of transcription, alters circadian rhythms through the light entrainment pathway. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289 (3): R656-662. doi: 10.1152/ ajpregu.00179. 2005.
136. Elesela S, Morris SB, Narayanan S, Kumar S, Lombard DB, Lukacs NW (2020) Sirtuin 1 regulates mitochondrial function and immune homeostasis in respiratory syncytial virus infected dendritic cells. PLoS Pathog. 16 (2): e1008319. doi: 10.1371/journal.ppat.1008319.
137. Pontes GN, Cardoso EC, Carneiro-Sampaio MM, Markus RP (2007) Pineal melatonin and the innate immune response: the TNF-alpha increase after cesarean section suppresses nocturnal melatonin production. J. Pineal Res. 43 (4): 365-371. doi: 10.1111/j.1600-079X.2007.00487.x.
138. Kido H, Indalao IL, Kim H, Kimoto T, Sakai S, Takahashi E (2016) Energy metabolic disorder is a major risk factor in severe influenza virus infection: Proposals for new therapeutic options based on animal model experiments. Respir. Investig. 54 (5): 312-319. doi: 10.1016/j.resinv.2016.02.007.
139. Wu HM, Zhao CC, Xie QM, Xu J, Fei GH (2020) TLR2-melatonin feedback loop regulates the activation of NLRP3 inflammasome in murine allergic airway inflammation. Front. Immunol. 11: 172. doi: 10.3389/fimmu.2020. 00172.
140. Zhao C, Zhao W (2020) NLRP3 inflammasome-a key player in antiviral responses. Front. Immunol. 11: 211. doi: 10.3389/fimmu.2020.00211.
141. Wang W, Li G, De Wu, Luo Z, Pan P, Tian M, Wang Y, Xiao F, Li A, Wu K, Liu X, Rao L, Liu F, Liu Y, Wu J (2018) Zika virus infection induces host inflammatory responses by facilitating NLRP3 inflammasome assembly and interleukin-1β secretion. Nat. Commun. 9 (1): 106. doi: 10.1038/s41467-017-02645-3.
142. Boule LA, Burke CG, Jin GB, Lawrence BP (2018) Aryl hydrocarbon receptor signaling modulates antiviral immune responses: ligand metabolism rather than chemical source is the stronger predictor of outcome. Sci. Rep. 8 (1): 1826. doi: 10.1038/s41598-018-20197-4.
143. Anderson G (2022) Tumor microenvironment and metabolism: Role of the mitochondrial melatonergic pathway in determining intercellular interactions in a new dynamic homeostasis. Int. J. Mol. Sci. 24 (1): 311. doi: 10.3390/ijms24010311.
144. Grunewald ME, Shaban MG, Mackin SR, Fehr AR, Perlman S (2020) Murine coronavirus infection activates the aryl hydrocarbon receptor in an indoleamine 2,3-dioxygenase-independent manner, contributing to cytokine modulation and proviral TCDD-inducible-PARP expression. J. Virol. 94 (3): e01743-19. doi: 10.1128/JVI.01743-19.
145. Kurupati RK, Kossenkoff A, Kannan S, Haut LH, Doyle S, Yin X, Schmader KE, Liu Q, Showe L, Ertl HCJ (2017) The effect of timing of influenza vaccination and sample collection on antibody titers and responses in the aged. Vaccine 35 (30): 3700-3708. doi: 10.1016/j.vaccine.2017.05.074.
146. de Bree LCJ, Mourits VP, Koeken VA, Moorlag SJ, Janssen R, Folkman L, Barreca D, Krausgruber T, Fife-Gernedl V, Novakovic B, Arts RJ, Dijkstra H, Lemmers H, Bock C, Joosten LA, van Crevel R, Benn CS, Netea MG (2020) Circadian rhythm influences induction of trained immunity by BCG vaccination. J. Clin. Invest. 130 (10): 5603-5617. doi: 10.1172/JCI133934.
147. Wang W, Balfe P, Eyre DW, Lumley SF, O'Donnell D, Warren F, Crook DW, Jeffery K, Matthews PC, Klerman EB, McKeating JA (2022) Time of day of vaccination affects SARS-CoV-2 antibody responses in an observational study of health ware Workers. J. Biol. Rhythms. 37 (1): 124-129. doi: 10.1177/074873042 11059315.
148. Grebe KM, Takeda K, Hickman HD, Bailey AL, Embry AC, Bennink JR, Yewdell JW (2010) Cutting edge: Sympathetic nervous system increases proinflammatory cytokines and exacerbates influenza A virus pathogenesis. J. Immunol. 184 (2): 540-544. doi: 10.4049/jimmunol.0903395.
149. Fujiwara S, Hoshizaki M, Ichida Y, Lex D, Kuroda E, Ishii KJ, Magi S, Okada M, Takao H, Gandou M, Imai H, Hara R, Herzog H, Yoshimura A, Okamura H, Penninger JM, Slutsky AS, Uhlig S, Kuba K, Imai Y (2019) Pulmonary phagocyte-derived NPY controls the pathology of severe influenza virus infection. Nat. Microbiol. 4 (2): 258-268. doi: 10.1038/s41564-018-0289-1.
150. Gergalova G, Lykhmus O, Kalashnyk O, Koval L, Chernyshov V, Kryukova E, Tsetlin V, Komisarenko S, Skok M (2012) Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria. PLoS One. 7 (2): e31361. doi: 10.1371/journal.pone.0031361.
151. Anderson G, Maes M (2020) Gut dysbiosis dysregulates central and systemic homeostasis via suboptimal mitochondrial function: Assessment, treatment and classification implications. Curr. Top. Med. Chem. 20 (7): 524-539. doi: 10.2174/1568 026620666200131094445.
152. Anderson G, Reiter RJ (2020) COVID-19 pathophysiology: interactions of gut microbiome, melatonin, vitamin D, stress, kynurenine and the alpha 7 nicotinic receptor: Treatment implications. Melatonin Res. 3 (3): 322-345. doi: 10.32794/ mr11250066.
153. Anderson G (2019) Gut dysbiosis dysregulates central and systemic homeostasis via decreased melatonin and suboptimal mitochondria functioning: pathoetiological and pathophysiological implications. Melatonin Res. 2 (2): 70-85. doi:10.32794/mr11250022.
154. Jin CJ, Engstler AJ, Sellmann C, Ziegenhardt D, Landmann M, Kanuri G, Lounis H, Schröder M, Vetter W, Bergheim I (2016) Sodium butyrate protects mice from the development of the early signs of non-alcoholic fatty liver disease: role of melatonin and lipid peroxidation. Br. J. Nutr. 116 (10): 1682-1693. doi: 10.1017/S0007114516004025.
155. Anderson G (2019) Daytime orexin and night-time melatonin regulation of mitochondria melatonin: roles in circadian oscillations systemically and centrally in breast cancer symptomatology. Melatonin Res. 2 (4): 1-8. doi: 10.32794/mr11250037.
156. Yagi K, Ishii M, Namkoong H, Fujii H, Asami T, Suzuki S, Asakura T, Mizoguchi K, Kamo T, Tasaka S, Iwata S, Kunkel SL, Hasegawa N, Betsuyaku T (2016) Histone deacetylase inhibition protects mice against lethal postinfluenza Pneumococcal infection. Crit. Care Med. 44 (10): e980-7. doi: 10.1097/CCM.
157. Shi Z, Gewirtz AT (2018) Together forever: Bacterial-viral interactions in infection and immunity. Viruses 10 (3): 122. doi: 10.3390/v10030122.
158. Perrin-Cocon L, Aublin-Gex A, Sestito SE, Shirey KA, Patel MC, André P, Blanco JC, Vogel SN, Peri F, Lotteau V (2017) TLR4 antagonist FP7 inhibits LPS-induced cytokine production and glycolytic reprogramming in dendritic cells, and protects mice from lethal influenza infection. Sci. Rep. 7: 40791. doi: 10.1038/srep40791.
159. Chen Y, Sun H, Bai Y, Zhi F (2019) Gut dysbiosis-derived exosomes trigger hepatic steatosis by transiting HMGB1 from intestinal to liver in mice. Biochem. Biophys. Res. Commun. 509 (3): 767-772. doi: 10.1016/j.bbrc.2018. 12.180.
160. Tekin S, Keske S, Alan S, Batirel A, Karakoc C, Tasdelen-Fisgin N, Simsek-Yavuz S, Isler B, Aydin M, Kapmaz M, Yilmaz-Karadag F, Ergonul O (2015) Predictors of fatality in influenza A virus subtype infections among inpatients in the 2015-2016 season. Int. J. Infect. Dis. 81: 6-9. doi: 10.1016/j.ijid.2019.01.005.
161. Chellappa SL, Vujovic N, Williams JS, Scheer FAJL (2019) Impact of circadian disruption on cardiovascular function and disease. Trends Endocrinol. Metab. 30 (10): 767-779. doi: 10.1016/j.tem.2019.07.008.
162. Geto Z, Molla MD, Challa F, Belay Y, Getahun T (2020) Mitochondrial dynamic dysfunction as a main triggering factor for inflammation associated chronic non-communicable diseases. J. Inflamm Res. 13: 97-107. doi: 10.2147/JI R.S232009.
163. Anderson G, Mazzoccoli G (2019) Left ventricular hypertrophy: Roles of mitochondria CYP1B1 and melatonergic pathways in coordinating wider pathophysiology. Int. J. Mol. Sci. 20 (16): 4068. doi: 10.3390/ijms20164068.
164. Mok JX, Ooi JH, Ng KY, Koh RY, Chye SM (2019) A new prospective on the role of melatonin in diabetes and its complications. Horm. Mol. Biol. Clin. Investig. 40 (1). doi:10.1515/hmbci-2019-0036.
165. Liu A, Lv H, Wang H, Yang H, Li Y, Qian J (2020) Aging increases the severity of colitis and the related changes to the gut barrier and gut microbiota in humans and mice. J. Gerontol. A Biol. Sci. Med. Sci. 75 (7): 1284-1292. doi: 10.1093/gerona/glz263.
166. Reiter RJ, Tan DX, Rosales-Corral S, Galano A, Zhou XJ, Xu B (2018) Mitochondria: Central organelles for melatonin's antioxidant and anti-aging actions. Molecules 23 (2): 509. doi: 10.3390/molecules23020509.
167. Chacon N, Chacín-Bonilla L, Cesari IM (2021) Implications of helminth immunomodulation on COVID-19 co-infections. Life Res. 4 (3): 26. doi: 10.5338 8/life 2021-0502-309.
168. Gutman JR, Lucchi NW, Cantey PT, Steinhardt LC, Samuels AM, Kamb ML, Kapella BK, McElroy PD, Udhayakumar V, Lindblade KA (2020) Malaria and parasitic neglected tropical diseases: Potential syndemics with COVID-19? Am. J. Trop. Med. Hyg. 103 (2): 572-577. doi: 10.4269/ajtmh.20-0516.
169. León-Figueroa DA, Abanto-Urbano S, Olarte-Durand M, Nuñez-Lupaca JN, Barboza JJ, Bonilla-Aldana DK, Yrene-Cubas RA, Rodriguez-Morales AJ (2022) COVID-19 and dengue coinfection in Latin America: A systematic review. New Microbes New Infect. 49: 101041. doi: 10.1016/j.nmni.2022.101041.
170. Kaur U, Jethwani P, Mishra S, Dehade A, Yadav AK, Chakrabarti S, Chakrabarti SS (2023) Did COVID-19 or COVID-19 vaccines influence the patterns of dengue in 2021? An exploratory analysis of two observational studies from North India. Am. J. Trop. Med. Hyg. 109 (6): 1290-1297. doi: 10.4269/ajtmh.23-0418.
171. Gouda MA, AboShabaan HS, Abdelgawad AS, Abdel Wahed AS, A Abd El-Razik K, Elsaadawy Y, Abdel-Wahab AA, Hawash Y (2023) Association between breakthrough infection with COVID-19 and Toxoplasma gondii: a cross-sectional study. Sci. Rep. 13 (1): 17636. doi: 10.1038/s41598-023-44616-3.
172. Chacín-Bonilla L, Chacon-Fonseca N, Rodriguez-Morales A (2021) Emerging issues in COVID-19 vaccination in tropical areas: Impact of the immune response against helminths in endemic areas. Travel Med. Infect. Dis. 42: 102087. doi: 10.1016/j.t maid.2021.102087.
173. Chacín-Bonilla L (2021) SARS-CoV-2: Potential feco-oral transmission and implications on the spread and severity of COVID-19 in Venezuela. Invest. Clín. 62 (Suppl. 2): 58-68. doi: 10.22209/IC.v62s2a05.
174. Ramírez JD, Sordillo EM, Gotuzzo E, Zavaleta C, Caplivski D, Navarro JC, Crainey JL, Bessa Luz SL, Noguera LAD, Schaub R, Rousseau C, Herrera G, Oliveira-Miranda MA, Quispe-Vargas MT, Hotez PJ, Paniz Mondolfi A (2020) SARS-CoV-2 in the Amazon region: A harbinger of doom for Amerindians. PLoS Negl. Trop. Dis. 14 (10): e0008686. doi: 10.1371/journal.pntd.0008686.
175. Chacín-Bonilla L, Mathews H, Dikdan Y, Guanipa N (1990) Estudio seroepidemiológico de la amibiasis en una comunidad del estado Zulia, Venezuela. Rev. Inst. Med. Trop. Sao Paulo 32 (6): 467-473.
176. Chacín-Bonilla L (1995) Criptosporidiosis en humanos. Invest. Clín. 36 (4): 207-250, 1995.
177. Chacín-Bonilla L, Sánchez Y, Estévez J, Larreal Y, Molero E (2003) Prevalence of human toxoplasmosis in San Carlos Island, Venezuela. Interciencia 28 (8): 457-462.
178. Chacín-Bonilla L (2010) Amibiasis: implicaciones del reconocimiento de Entamoeba dispar e identificación de Entamoeba moshkovskii en humanos Invest. Clín. 51 (2): 239-256.
179. Chacín-Bonilla L (2017) Perfil epidemiológico de las enfermedades infecciosas en Venezuela. Invest. Clín. 58 (2): 103-105.
180. Fonte L, Acosta A, Sarmiento ME, Ginori M, García G, Norazmi MN (2020) COVID-19 lethality in Sub-Saharan Africa and helminth immune modulation. Front. Immunol. 11: 574910. doi: 10.3389/fimmu.2020.574910.
181. Harris NL, Loke P (2017) Recent advances in type-2-cell-mediated immunity: Insights from helminth infection. Immunity 47 (6): 1024-1036. doi: 10.1016/j.immuni.2017.11.01 015.
182. Siles-Lucas M, González-Miguel J, Geller R, Sanjuan R, Pérez-Arévalo J, Martínez-Moreno Á (2021) Potential influence of helminth molecules on COVID-19 pathology. Trends Parasitol. 37 (1): 11-14. doi: 10.1016/j.pt.2020.10.002.
183. Bradbury RS, Piedrafita D, Greenhill A, Mahanty S (2020) Will helminth co-infection modulate COVID-19 severity in endemic regions? Nat. Rev. Immunol. 20 (6): 342. doi: 10.1038/s41577-020-0330-5.
184. Rick F, Odoke W, van den Hombergh J, Benzaken AS, Avelino-Silva VI (2022) Impact of coronavirus disease (COVID-19) on HIV testing and care provision across four continents. HIV Med. 23 (2): 169-177. doi: 10.1111/hiv. 13180.
185. Chacín-Bonilla L (2021) Criptosporidiosis en personas infectadas por el VIH en Venezuela: Potencial impacto de la crisis en el país. Invest. Clín. 62 (1): 1-3. doi: 10.22209/IC.v62n1a00.
186. Chacín-Bonilla L (2023) Las enfermedades tropicales desatendidas en Venezuela en la era de COVID-19. Invest. Clín. 64 (1): 1-3. doi: 10.54817/IC.v 64n1a00.
187. Root-Bernstein R (2023) From co-infections to autoimmune disease via hyperactivated innate immunity: COVID-19 autoimmune coagulopathies, autoimmune myocarditis and multisystem inflammatory syndrome in children. Int. J. Mol. Sci. 24 (3): 3001. doi: 10.3390/ijms24033001.
188. Salam N, Azam S (2017) Prevalence and distribution of soil-transmitted helminth infections in India. BMC Public Health 17 (1): 201. doi: 10.1186/s 12889-017-4113-2.
189. Maizels RM, Smits HH, McSorley HJ (2018) Modulation of host immunity by helminths: The expanding repertoire of parasite effector molecules. Immunity 49 (5): 801-818. doi: 10.1016/j.immuni.2018.10.016.
190. Chacín-Bonilla L, Dikdan Y (1981) Prevalencia de Entamoeba histolytica y otros parásitos intestinales en una comunidad suburbana de Maracaibo. Invest. Clín. 22 (4): 185-203.
191. Chacín-Bonilla L (1985) Geohelmintiasis in Venezuela: Un viejo y grave problema que tiende a persistir. Invest. Clín. 26 (1): 1 3.
192. Chacín-Bonilla L, Dikdan Y, Guanipa N, Villalobos R (1990) Prevalencia de Entamoeba histolytica y otros parásitos intestinales en un barrio del municipio Mara, estado Zulia, Venezuela. Invest. Clín. 31 (1): 3 15.
193. Chacín-Bonilla L, Guanipa N, Cano G, Parra AM, Estévez J, Raleigh X (1998) Epidemiological study of intestinal parasitic infections in a rural area from Zulia State, Venezuela. Interciencia 23 (4): 241-247, 1998.
194. Paniz-Mondolfi AE, Ramírez JD, Delgado-Noguera LA, Rodriguez-Morales AJ, Sordillo EM (2021) COVID-19 and helminth infection: Beyond the Th1/Th2 paradigm. PLoS Negl. Trop. Dis. 15 (5): e0009402. doi: 10.1371/ journal.pntd.0009402.
195. Kumar S, Nyodu R, Maurya VK, Saxena SK (2020) Host immune response and immunobiology of human SARS-CoV-2 infection. Coronavirus disease 2019 (COVID-19). 30: 43-53. doi: 10.1007/978-981-15-4814-7_5.
196. O'Neill LAJ, Netea MG (2020) BCG-induced trained immunity: can it offer protection against COVID-19? Nat. Rev. Immunol. 20 (6): 335-337. doi: 10.1038/s41577-020-0337-y.
197. Stettler K, Beltramello M, Espinosa DA, Graham V, Cassotta A, Bianchi S, Vanzetta F, Minola A, Jaconi S, Mele F, Foglierini M, Pedotti M, Simonelli L, Dowall S, Atkinson B, Percivalle E, Simmons CP, Varani L, Blum J, Baldanti F, Cameroni E, Hewson R, Harris E, Lanzavecchia A, Sallusto F, Corti D (2016) Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection. Science. 353 (6301): 823-826. doi: 10.1126/science.aaf8505.
198. Wen J, Shresta S (2019) Antigenic cross-reactivity between Zika and dengue viruses: is it time to develop a universal vaccine? Curr. Opin. Immunol. 59: 1-8. doi: 10.1016/j. coi.2019.02.001.
199. Wait LF, Dobson AP, Graham AL (2020) Do parasite infections interfere with immunisation? A review and meta-analysis. Vaccine 38 (35): 5582-5590. doi: 10.1016/j.vaccine.2020.06.064.
200. Jeyanathan M, Afkhami S, Smaill F, Miller MS, Lichty BD, Xing Z (2020) Immunological considerations for COVID-19 vaccine strategies. Nat. Rev. Immunol. 20 (10): 615-632. doi: 10.1038/s41577-020-00434-6.
201. Taylor-Robinson DC, Maayan N, Donegan S, Chaplin M, Garner P (2019) Public health deworming programs for soil-transmitted helminths in children living in endemic areas. Cochrane Database Syst. Rev. 9 (9): CD000371. doi: 10.1002/14651858. CD000371.pub7.
202. Tan DX, Reiter RJ (2022) Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality. Life Sci. 294:120368. doi: 10.1016/j.lfs.2022.120368.
Published
2024-08-01
How to Cite
[1]
Chacin-Bonilla, L. and Bonilla, E. 2024. Multiple actions of melatonin in reducing viral pathophysiologies. Melatonin Research. 7, 2 (Aug. 2024), 153-180. DOI:https://doi.org/https://doi.org/10.32794/mr112500173.