In response to the COVID-19 pandemic, and the lack of effective and safe antivirals against it, we adopted a new approach in which food supplements with vital antiviral characteristics, low toxicity, and fast excretion have been targeted. The structures and chemical properties of the food supplements were compared to the promising antivirals against SARS-COV-2. Our goal was to exploit the food supplements to mimic the topical antivirals' functions but circumventing their severe side effects, which has limited the necessary dosage needed to exhibit the desired antiviral activity. On this line, after a comparative structural analysis of the chemicals mentioned above, and investigation of their potential mechanisms of action, we selected caffeine and some compounds of the vitamin B family and further applied molecular modeling techniques to evaluate their interactions with the RDB domain of the Spike protein of SARS-CoV-2 (SC2Spike) and its corresponding binding site on human ACE-2 (HssACE2). Our results pointed to vitamins B1 and B6 in the neutral form as potential binders to the HssACE2 RDB binding pocket that might be able to impair the SARS-CoV-2 mechanism of cell invasion, qualifying as potential leads for experimental investigation against COVID-19.

• Klíčová slova
• COVID-19, Caffeine, Docking, Molecular dynamic simulations, Vitamin B,
• MeSH
• antivirové látky farmakologie   chemie   MeSH
• farmakoterapie COVID-19 * MeSH
• kofein farmakologie   MeSH
• lidé MeSH
• niacinamid MeSH
• pandemie MeSH
• pyridoxamin MeSH
• racionální návrh léčiv MeSH
• SARS-CoV-2 MeSH
• simulace molekulového dockingu MeSH
• thiamin metabolismus   MeSH
• vitaminy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky MeSH
• kofein MeSH
• niacinamid MeSH
• pyridoxamin MeSH
• thiamin MeSH
• vitaminy MeSH

• Klíčová slova
• HPLC, Human whole blood, Pyridoxal-5-phosphate, Thiamine derivatives, Vitamin status,
• MeSH
• aplikace orální MeSH
• biochemická analýza krve metody   MeSH
• dospělí MeSH
• kalibrace MeSH
• lidé MeSH
• pyridoxalfosfát krev   MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• thiamin aplikace a dávkování   krev   metabolismus   MeSH
• thiaminmonofosfát krev   MeSH
• thiaminpyrofosfát krev   MeSH
• vitamin B6 krev   metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie přístrojové vybavení   metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• pyridoxalfosfát MeSH
• thiamin MeSH
• thiaminmonofosfát MeSH
• thiaminpyrofosfát MeSH
• vitamin B6 MeSH

AIM: Pentose phosphate pathway (PPP) with key enzyme transketolase (TKT), represents a potentially 'protective' mechanism in hyperglycaemia. Diabetic kidney disease (DKD), a common complication of both type 1 and type 2 diabetes associated with significant morbidity and mortality, represents the most common cause of chronic kidney disease (CKD). We hypothesized that protective PPP action in diabetes and eventually even more severely in concomitant DKD might be compromised by limited intracellular availability of an active TKT cofactor thiamine diphosphate (TDP). METHODS: Effect of hyperglycaemia on gene expression and protein levels of key PPP loci was studied in vitro using human cell lines relevant to diabetes (HUVEC and HRGEC) and (together with measurement of TKT activity, plasma thiamine and erythrocyte TDP concentration) in vivo in diabetic vs. non-diabetic subjects with comparable renal function (n=83 in total). RESULTS: Hyperglycaemia significantly decreased protein levels of RFC-1, THTR1, THTR2 and TKT (P<0.05) in vitro. Analysis of blood samples from CKD patients with and without diabetes and from controls did not reveal any difference in gene expression and protein levels of thiamine transporters while TKT activity and TDP in erythrocytes gradually increased with decreasing kidney function being highest in patients with CKD3-4 of both diabetic and non-diabetic aetiology. Hyperglycaemia and uremic serum mimicking CKD in diabetes did not affect TKT activity in vitro (P<0.05). CONCLUSION: Both in vitro and human experiments showed decrease or unchanged expression, respectively, of thiamine transporters induced by hyperglycaemia while TKT activity in parallel with intracellular TDP was increased in CKD patients with or without diabetes. Therefore, lack of adaptive increase of thiamine transmembrane transport allowing further increase of TKT activity might contribute to compromised PPP function in diabetes and CKD and to the development of glycotoxic injury.

• MeSH
• biologický transport MeSH
• chronická renální insuficience metabolismus   MeSH
• diabetes mellitus 2. typu metabolismus   MeSH
• diabetické nefropatie metabolismus   MeSH
• dospělí MeSH
• erytrocyty metabolismus   MeSH
• hyperglykemie metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• thiamin metabolismus   MeSH
• transketolasa metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• thiamin MeSH
• transketolasa MeSH

BACKGROUND: Pentose phosphate pathway (PPP) represents a potentially 'protective' mechanism in hyperglycaemia due to shunting of glycolytic intermediates into PPP reactions. We hypothesized that thiamine status (plasma and erythrocyte levels of thiamine and its esters) together with genetic variability in key PPP enzymes-transketolase (TKT), transaldolase and TKT-like-might contribute to the progression of diabetic nephropathy (DN) and mortality of diabetics. METHODS: A total of 240 diabetic subjects with variable degree of kidney disease were included at baseline and were followed up for a median of 26 (IQR 21-50) months. Concentrations of thiamine in plasma and whole blood and TKT-catalysed reaction were determined by HPLC. Single-nucleotide polymorphisms (SNPs) (n = 14) were genotyped by means of PCR using TaqMan chemistry (Applied Biosystems, Foster City, CA, USA). RESULTS: Significant differences in pTh, pThDP, eryThDP and eryTKT between DN-stage groups were ascertained (P < 0.05) with advancing stage of DN being accompanied with increasing values of pTh, pThDP and eryTKT but not eryThDP. A highly significant negative correlation (r = - 0.41, P < 0.001) was found between pThDP and eryThDP, and the tertiles of the ratio of eryThDP/pThDP were significantly associated with all-cause mortality rates (P = 0.0072). We also identified significant differences in the rate of DN progression between different pTDP tertile groups (P = 0.0017). No significant genetic effects were found. CONCLUSIONS: The results support the role of 'functional' thiamine deficiency in the development of hyperglycaemia-related pathology. Limited intracellular availability of active TKT co-factor seems to be a dominant abnormality.

• MeSH
• diabetické nefropatie enzymologie   genetika   mortalita   MeSH
• dospělí MeSH
• erytrocyty enzymologie   MeSH
• genotyp MeSH
• glukosa metabolismus   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• následné studie MeSH
• pentosafosfáty metabolismus   MeSH
• pentózofosfátový cyklus MeSH
• průřezové studie MeSH
• senioři MeSH
• thiamin metabolismus   MeSH
• transaldolasa genetika   MeSH
• transketolasa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glukosa MeSH
• pentosafosfáty MeSH
• thiamin MeSH
• TKTL1 protein, human MeSH Prohlížeč
• transaldolasa MeSH
• transketolasa MeSH

A recessive mutation leading to complete loss of thiamine uptake in Saccharomyces cerevisiae was mapped on the left arm of chromosome VII, approximately 56 cM centromere-distal to trp5. As the analysed locus is relatively distant from its centromere and from the markers used, its attachment to chromosome VII was confirmed by chromosome loss methods.

• MeSH
• alely MeSH
• biologický transport MeSH
• geny hub * MeSH
• geny recesivní MeSH
• křížení genetické MeSH
• mapování chromozomů MeSH
• mutace MeSH
• Saccharomyces cerevisiae genetika   metabolismus   MeSH
• thiamin metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• thiamin MeSH

Neither exit nor counterflow efflux of thiamin, taken up previously by an active transport, were found in Saccharomyces cerevisiae, in either the wild type or a mutant with a lower rate of thiamin phosphorylation. Complete inhibition of thiamin phosphorylation by oxythiamin did not lead to any release of thiamin taken up by the cell.

• MeSH
• aktivní transport účinky léků   MeSH
• fosforylace MeSH
• kinetika MeSH
• mutace MeSH
• oxythiamin farmakologie   MeSH
• Saccharomyces cerevisiae genetika   růst a vývoj   metabolismus   MeSH
• thiamin antagonisté a inhibitory   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• oxythiamin MeSH
• thiamin MeSH

• MeSH
• cykasin metabolismus   MeSH
• dietní proteiny metabolismus   MeSH
• dietní sacharidy metabolismus   MeSH
• dietní tuky metabolismus   MeSH
• esenciální mastné kyseliny metabolismus   MeSH
• fyziologie výživy * MeSH
• galaktosidasy metabolismus   MeSH
• gnotobiologické modely * MeSH
• králíci MeSH
• krysa rodu Rattus MeSH
• minerály metabolismus   MeSH
• morčata MeSH
• myši MeSH
• proteasy metabolismus   MeSH
• steroly metabolismus   MeSH
• střeva mikrobiologie   MeSH
• střevní sliznice metabolismus   MeSH
• thiamin metabolismus   MeSH
• vitamin A metabolismus   MeSH
• žlučové kyseliny a soli metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• krysa rodu Rattus MeSH
• morčata MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cykasin MeSH
• dietní proteiny MeSH
• dietní sacharidy MeSH
• dietní tuky MeSH
• esenciální mastné kyseliny MeSH
• galaktosidasy MeSH
• minerály MeSH
• proteasy MeSH
• steroly MeSH
• thiamin MeSH
• vitamin A MeSH
• žlučové kyseliny a soli MeSH

A naturally deficient thiamine and methionine requiring strain of Bacillus coagulans (Ms 5) accumulates lysine in medium only when exogenous pyridoxine (optimal concentration, 0.1 mu g/ml) are supplied. Threonine exerts an inhibitory effect at higher concentrations but pyridoxine does not.

• MeSH
• Bacillus klasifikace   růst a vývoj   metabolismus   MeSH
• kolorimetrie MeSH
• lysin biosyntéza   MeSH
• methionin metabolismus   MeSH
• mutace * MeSH
• papírová chromatografie MeSH
• pyridoxin metabolismus   MeSH
• thiamin metabolismus   MeSH
• threonin metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lysin MeSH
• methionin MeSH
• pyridoxin MeSH
• thiamin MeSH
• threonin MeSH

• MeSH
• dospělí MeSH
• fyziologický stres metabolismus   MeSH
• kyselina askorbová metabolismus   MeSH
• lidé MeSH
• spánková deprivace MeSH
• thiamin metabolismus   MeSH
• vysoká teplota MeSH
• železo metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• kyselina askorbová MeSH
• thiamin MeSH
• železo MeSH

• MeSH
• histocytochemie MeSH
• mozková kůra patologie   MeSH
• nekróza patologie   MeSH
• nemoci centrálního nervového systému veterinární   MeSH
• nemoci skotu patologie   MeSH
• skot MeSH
• thiamin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Československo MeSH
• Názvy látek
• thiamin MeSH