Ebola virus disease: Potential use of melatonin as a treatment.
Tan DX1, Reiter RJ, Manchester LC.
The purpose of this report is to emphasize the potential utility for the use of melatonin in the treatment of individuals who are infected with the Ebola virus. The pathological changes associated with an Ebola infection include, most notably, endothelial disruption, dissiminated intravascular coagulation and multiple organ hemorrhage. Melatonin has been shown to target these alterations. Numerous similarities between Ebola virus infection and septic shock have recognized for more than a decade. Moreover, melatonin has been successfully employed for the treatment of sepsis in many experimental and clinical studies. Based on these factors, since the number of treatments currently available is limited and the useable products are not abundant, the use of melatonin for the treatment of Ebola virus infection is encouraged. Additionally, melatonin has a high safety profile, is readily-available and can be orally-self administered; thus, the use of melatonin is compatible with the large scale of this serious outbreak.
Re: Clinical trials of Ebola treatment to start in Africa
Although direct antiviral treatments through passive immunity would certainly have potential for treating Ebola, it’s not the virus which kills, but rather the damaged immune system discharging a “cytokine storm” and large amounts of nitric oxide, damaging blood vessels, causing blood and plasma leakage and dangerously low blood pressure similar to severe septic shock (1).
Treatment with melatonin might have some potential for alleviating the morbidity and mortality of Ebola virus infection, since melatonin has immuno-modulating and inhibitory functions against production and activation of pro-inflammatory mediators such as cytokines as well as preventing multiple organ and circulatory failure in septic shock and also has antiviral actions (2).
Ebola also causes coagulation abnormalities leading to hemorrhage through dramatically increased levels of tissue factor from lymphoid macrophages (3).
Melatonin stimulates release of a tissue factor pathway inhibitor from the vascular endothelium, which could potentially reduce bleeding complications from excessive tissue factor release (4).
Since melatonin has virtually no toxicity, along with conventional therapy (5), it would appear to have potential for treatment of ebola viral infection, to reduce complications such as organ failure, bleeding and shock, and possibly could reduce the mortality rate.
1. http://www.npr.org/blogs/goatsandsoda/2 ... -ebola-kil...
2. Srinivasan V, Mohamed M, Kato H. Melatonin in bacterial and viral infections with focus on sepsis: a review. Recent Pat Endocr Metab Immune Drug Discov. 2012; 6: 30-39.
3. Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE. Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis 2003; 188: 1618-1629.
4. Kostovski E, Dahm AE, Iversen N, Hieltnes N, Osterud B, Sandset PM, Iversen PO. Melatonin stimulates release of tissue factor pathway inhibitor from the vascular endothelium. Blood Coagul Fibrinolysis. 2011; 22: 254-259.
5. Escames G, Acuna-Castroveijo D, Lopez LC, Tan DX, Maldonado MD, Sanchez-Hidalgo M, Leon J, Reiter RJ. Pharmacological utility of melatonin in the treatment of septic shock: experimental and clinical evidence. J Pharm Pharmacol. 2006; 58: 1153-1165.
Más sobre melatonina
http://onlinelibrary.wiley.com/doi/10.1 ... 9/abstract
Este mismo año se ha hecho uno de los primeros estudios usando vitamina C en sepsisAscorbic acid inhibits the multiplication of viruses of widely different structures, i.e., regardless of enveloped or nonenveloped, double-stranded DNA or single-stranded RNA genome, and regardless whether the replication and transcription of the viral genome occur in the nucleus or in the cytoplasm of the infected cells
Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis.
Fowler AA 3rd1, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, Farthing CA, Larus TL, Martin E, Brophy DF, Gupta S; Medical Respiratory Intensive Care Unit Nursing, Fisher BJ, Natarajan R.
Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis.
Twenty-four patients with severe sepsis in the medical intensive care unit were randomized 1:1:1 to receive intravenous infusions every six hours for four days of ascorbic acid: Lo-AscA (50 mg/kg/24 h, n = 8), or Hi-AscA (200 mg/kg/24 h, n = 8), or Placebo (5% dextrose/water, n = 8). The primary end points were ascorbic acid safety and tolerability, assessed as treatment-related adverse-event frequency and severity. Patients were monitored for worsened arterial hypotension, tachycardia, hypernatremia, and nausea or vomiting. In addition Sequential Organ Failure Assessment (SOFA) scores and plasma levels of ascorbic acid, C-reactive protein, procalcitonin, and thrombomodulin were monitored.
Mean plasma ascorbic acid levels at entry for the entire cohort were 17.9 ± 2.4 μM (normal range 50-70 μM). Ascorbic acid infusion rapidly and significantly increased plasma ascorbic acid levels. No adverse safety events were observed in ascorbic acid-infused patients. Patients receiving ascorbic acid exhibited prompt reductions in SOFA scores while placebo patients exhibited no such reduction. Ascorbic acid significantly reduced the proinflammatory biomarkers C-reactive protein and procalcitonin. Unlike placebo patients, thrombomodulin in ascorbic acid infused patients exhibited no significant rise, suggesting attenuation of vascular endothelial injury.
Intravenous ascorbic acid infusion was safe and well tolerated in this study and may positively impact the extent of multiple organ failure and biomarkers of inflammation and endothelial injury.
Vitamin C Is an Essential Factor on the Anti-viral Immune Responses through the Production of Interferon-α/β at the Initial Stage of Influenza A Virus (H3N2) Infection
L-ascorbic acid (vitamin C) is one of the well-known anti-viral agents, especially to influenza virus. Since the in vivo anti-viral effect is still controversial, we investigated whether vitamin C could regulate influenza virus infection in vivo by using Gulo (-/-) mice, which cannot synthesize vitamin C like humans. First, we found that vitamin C-insufficient Gulo (-/-) mice expired within 1 week after intranasal inoculation of influenza virus (H3N2/Hongkong). Viral titers in the lung of vitamin C-insufficient Gulo (-/-) mice were definitely increased but production of anti-viral cytokine, interferon (IFN)-α/β, was decreased. On the contrary, the infiltration of inflammatory cells into the lung and production of pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-α/β, were increased in the lung. Taken together, vitamin C shows in vivo anti-viral immune responses at the early time of infection, especially against influenza virus, through increased production of IFN-α/β.
Antiviral effects of ascorbic and dehydroascorbic acids in vitroSuppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells.
Harakeh S1, Jariwalla RJ, Pauling L.
We have studied the action of ascorbate (vitamin C) on human immunodeficiency virus type 1 (HIV-1), the etiological agent clinically associated with AIDS. We report the suppression of virus production and cell fusion in HIV-infected T-lymphocytic cell lines grown in the presence of nontoxic concentrations of ascorbate. In chronically infected cells expressing HIV at peak levels, ascorbate reduced the levels of extracellular reverse transcriptase (RT) activity (by greater than 99%) and of p24 antigen (by 90%) in the culture supernatant. Under similar conditions, no detectable inhibitory effects on cell viability, host metabolic activity, and protein synthesis were observed. In freshly infected CD4+ cells, ascorbate inhibited the formation of giant-cell syncytia (by approximately 93%). Exposure of cell-free virus to ascorbate at 37 degrees C for 1 day had no effect on its RT activity or syncytium-forming ability. Prolonged exposure of virus (37 degrees C for 4 days) in the presence of ascorbate (100-150 micrograms/ml) resulted in the drop by a factor of 3-14 in RT activity as compared to a reduction by a factor of 25-172 in extracellular RT released from chronically infected cells. These results indicate that ascorbate mediates an anti-HIV effect by diminishing viral protein production in infected cells and RT stability in extracellular virions.
Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells
Antiviral Lectins from Red and Blue-Green Algae Show Potent In Vitro and In Vivo Activity against Hepatitis C Virus
http://www.plosone.org/article/info%3Ad ... ne.0064449
Isolation and Characterization of Griffithsin, a Novel HIV-inactivating Protein, from the Red Alga Griffithsia sp
Plant lectins are potent inhibitors of coronaviruses by interfering with two targets in the viral replication cycle
http://www.sciencedirect.com/science/ar ... 4207002380
High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection
N acetil cisteina
AjoN-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus.
Geiler J1, Michaelis M, Naczk P, Leutz A, Langer K, Doerr HW, Cinatl J Jr.
The antioxidant N-acetyl-L-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on virus replication, virus-induced pro-inflammatory responses and virus-induced apoptosis were investigated in H5N1-infected lung epithelial (A549) cells. NAC at concentrations ranging from 5 to 15 mM reduced H5N1-induced cytopathogenic effects (CPEs), virus-induced apoptosis and infectious viral yields 24 h post-infection. NAC also decreased the production of pro-inflammatory molecules (CXCL8, CXCL10, CCL5 and interleukin-6 (IL-6)) in H5N1-infected A549 cells and reduced monocyte migration towards supernatants of H5N1-infected A549 cells. The antiviral and anti-inflammatory mechanisms of NAC included inhibition of activation of oxidant sensitive pathways including transcription factor NF-kappaB and mitogen activated protein kinase p38. Pharmacological inhibitors of NF-kappaB (BAY 11-7085) or p38 (SB203580) exerted similar effects like those determined for NAC in H5N1-infected cells. The combination of BAY 11-7085 and SB203580 resulted in increased inhibitory effects on virus replication and production of pro-inflammatory molecules relative to either single treatment. NAC inhibits H5N1 replication and H5N1-induced production of pro-inflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.
Antiviral properties of garlic: in vitro effects on influenza B, herpes simplex and coxsackie viruses
Revisión extractos de hierbas vs distintos virus
http://www.irjponline.com/admin/php/upl ... 25_pdf.pdf
http://onlinelibrary.wiley.com/doi/10.1 ... .24575/pdf
Efectos adversos en megadosis de vitamina C: poca cosa.
http://www.plosone.org/article/info%3Ad ... 11414-g002
Están con lo de aprobar la vacuna experimental, que es probablemente lo que esté detrás de todo esto