Thiamine Disulfide as a Potent Inhibitor of Human Immunodeficiency Virus (Type-1) Production

Shoji, Shuichi; Furuishi, Kazuchika; Misumi, Shogo; Miyazaki, Tameo; Kino, Mitsutaka; Yamataka, Kazunobu

doi:10.1006/bbrc.1994.2760

Cited by 21 publications

(10 citation statements)

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“…Thiamine deficiency has been associated with immunosuppression in several investigations e.g. 22, as well as with increased parasite infestation23. Hence, it is interesting to note the negative relationship between the number of the swim bladder parasite Anguillicola crassus and proportion liver TDP in silver eels (Fig.…”

Section: Resultsmentioning

confidence: 92%

Widespread episodic thiamine deficiency in Northern Hemisphere wildlife

Balk

Hägerroth

Gustavsson

et al. 2016

Sci Rep

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Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiamine-dependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.

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Section: Resultsmentioning

confidence: 92%

Widespread episodic thiamine deficiency in Northern Hemisphere wildlife

Balk

Hägerroth

Gustavsson

et al. 2016

Sci Rep

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“…We derived an effective dose range of thiamine that could be administered for alleviating the Th17 cell proinflammatory response by using the IL-17 concentrations that we obtained from our AUD patients (termed as DC), levels found in the literature, and levels in the healthy control (HV) group. Thiamine has been administered as a treatment in other viral infections (Butterworth et al, 1991;Shoji et al, 1994), and has proven effective for some inflammatory conditions and symptoms (Wallace and Weeks, 2001;Kim et al, 2018). A well-structured treatment profile of thiamine based on the results of proof of concept in vitro experiments, and analyses of proinflammatory response-relevant disease conditions support the potential efficacy of thiamine in ameliorating the proinflammatory Th17 response in severe COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Repurposing Treatment of Wernicke–Korsakoff Syndrome for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-Vitro Evidence and Pharmacokinetic Profile

Vatsalya

Frimodig

et al. 2021

Front. Pharmacol.

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Coronavirus disease identified in 2019 (COVID-19) can be complicated by the Th17 cell-mediated IL-17 proinflammatory response. We tested if thiamine can effectively lower the Th17 response in a clinical study [Proinflammatory state in alcohol use disorder patients termed as disease controls (DC)] and corroborated the results using an in vitro study. We developed an effective dose range and model for key pharmacokinetic measures with the potential of targeting the cytokine storm and neurological symptoms of COVID-19. Three-week 200 mg dose of thiamine was administered to sixteen DC patients. Eight healthy volunteers (HV) were also included in this investigation. A subsequent in vitro study was performed to validate the effectiveness of thiamine [100 mg/day equivalent (0.01 μg/ml)] treatment in lowering the Th17 proinflammatory response in a mouse macrophage cell line (RAW264.7) treated with ethanol. Based on recent publications, we compared the results of the IL-17 response from our clinical and in vitro study to those found in other proinflammatory disease conditions (metabolic conditions, septic shock, viral infections and COVID-19) and effective and safe dose ranges of thiamine. We developed a pharmacokinetic profile for thiamine dose range as a novel intervention strategy in COVID-19. DC group showed significantly elevated proinflammatory cytokines compared to HV. Thiamine-treated DC patients showed significant lowering in IL-17 and increase in the IL-22 levels. In humans, a range of 79–474 mg daily of thiamine was estimated to be effective and safe as an intervention for the COVID-19 cytokine storm. A literature review showed that several neurological symptoms of COVID-19 (∼45.5% of the severe cases) occur in other viral infections and neuroinflammatory states that may also respond to thiamine treatment. Thiamine, a very safe drug even at very high doses, could be repurposed for treating the Th17 mediated IL-17 immune storm, and the subsequent neurological symptoms observed in COVID-19. Further studies using thiamine as an intervention/prevention strategy in COVID-19 patients could identify its precise anti-inflammatory role.

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“…22 Thiamine disulfide markedly inhibited the production of progeny HIV-1 in acutely and chronically HIV-1-infected cells. 23 These results suggest a relationship between thiamine and HIV. Therefore, we review the role of thiamine in HIV infection.…”

Section: Introductionmentioning

confidence: 89%

The role of thiamine in HIV infection

Lương

Nguyễn

2013

International Journal of Infectious Diseases

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Patients infected with HIV have a high prevalence of thiamine deficiency. Genetic studies have provided the opportunity to determine which proteins link thiamine to HIV pathology, i.e., renin-angiotensin system, poly(ADP-ribosyl) polymerase 1, Sp1 promoter gene, transcription factor p53, apoptotic factor caspase 3, and glycogen synthetase kinase 3β. Thiamine also affects HIV through non-genomic factors, i.e., matrix metalloproteinase, vascular endothelial growth factor, heme oxygenase 1, the prostaglandins, cyclooxygenase 2, reactive oxygen species, and nitric oxide. In conclusion, thiamine may benefit HIV patients, but further investigation of the role of thiamine in HIV infection is needed.

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Thiamine Disulfide as a Potent Inhibitor of Human Immunodeficiency Virus (Type-1) Production

Cited by 21 publications

References 0 publications

Widespread episodic thiamine deficiency in Northern Hemisphere wildlife

Widespread episodic thiamine deficiency in Northern Hemisphere wildlife

Repurposing Treatment of Wernicke–Korsakoff Syndrome for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-Vitro Evidence and Pharmacokinetic Profile

The role of thiamine in HIV infection

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