Enteroviruses have been associated with a host of clinical presentations including acute flaccid paralysis (AFP). The site of primary replication for most enteroviruses is the gastrointestinal tract (GIT) and lactic acid bacteria (LAB) may confer protection in the GIT against them. This study therefore investigates the antiviral potential of some selected lactic acid bacteria against enterovirus isolates recovered from AFP cases. The antiviral activities of Lactobacillus plantarum, Lactobacillus amylovorus, and Enterococcus hirae in broth culture, their cell-free supernatant (CFS), and bacterial cell pellets were assayed against Echovirus 7 (E7), E13, and E19 in a pre- and post-treatment approach using cytopathic effect (CPE) and cell viability (MTT) assay. The tested Lactobacillus plantarum, Lactobacillus amylovorus, and Enterococcus hirae strains have good antiviral properties against E7 and E19 but not against E13. Lactobacillus amylovorus AA099 shows the highest activity against E19. The pre-treatment approach displays better antiviral activities compared to post-treatment approach. The LAB in broth suspension have better antiviral activities than their corresponding CFS and bacterial pellet. Lactic acid bacteria used in this study have the potential as antiviral agents.
- MeSH
- antivirové látky farmakologie MeSH
- druhová specificita MeSH
- Enterococcus hirae fyziologie MeSH
- enterovirové infekce prevence a kontrola virologie MeSH
- Enterovirus klasifikace účinky léků MeSH
- Lactobacillales fyziologie MeSH
- Lactobacillus acidophilus fyziologie MeSH
- Lactobacillus plantarum fyziologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- probiotika farmakologie MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Honeybee viruses have been recognized as being among the most important factors leading to colony losses worldwide. Colony food and faeces are regarded as possible sources of infectious viruses able to contaminate the environment and equipment of apiaries. Thus, methods for elimination of viruses are required. No cell culture assay for testing the effect of disinfectants on honeybee viruses is yet available. Therefore, surrogate virus was employed for testing of the efficacy of iodophor- and peracetic acid-based disinfectants in combination with six organic contaminants at +6 °C and +22 °C. Moreover, we evaluated the persistence of the surrogate in honey at +6 °C, +22 °C, and +50 °C. RESULTS: Iodophor-based disinfectant showed a maximum reduction of virus titre of 3.4 log10. Peracetic acid reduced the titre (≥4 log10) only at 22 °C and without yeast extract/bovine serum albumin. After 25 days of incubation of the virus - honey mix, no decrease of virus titre was observed at +6 °C, whereas a significant reduction (3.5 log10) was found at +50 °C already after 1 day. CONCLUSIONS: Both tested disinfectants can serve as appropriate virucides in apiaries. The effect of peracetic acid significantly depended on temperature and organic contaminants. The iodophor-based disinfectant showed a stable antiviral effect at different temperatures and with different contaminants. © 2017 Society of Chemical Industry.
- MeSH
- antivirové látky farmakologie MeSH
- dezinficiencia farmakologie MeSH
- Enterovirus účinky léků fyziologie MeSH
- včelařství MeSH
- včely fyziologie virologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Enteroviruses rank among the most common human pathogens; millions of people suffer from diseases caused by them every year. However, no specific treatment of infections caused by this genus from the Picornaviridae family has been introduced to clinical practice so far. Therefore, a search for potential therapeutics aiming at these viruses is urgently needed. Due to advances in biochemistry and molecular biology, we are able to aim at specific viral proteins as well as possible host factors essential for virus replication in cells. Recently, a number of compounds inhibiting replication of various enteroviruses have been reported, based on both rational targetbased drug design and phenotypic screening. This article is a review of common structure patterns of the compounds that have been recently found to inhibit the replication of enteroviruses.
- MeSH
- antivirové látky farmakokinetika farmakologie chemie klasifikace MeSH
- Enterovirus fyziologie genetika růst a vývoj účinky léků ultrastruktura MeSH
- inhibitory proteas chemie MeSH
- klinická farmakologie metody trendy MeSH
- lidé MeSH
- Picornaviridae * fyziologie genetika růst a vývoj účinky léků ultrastruktura MeSH
- pikornavirové infekce * farmakoterapie genetika MeSH
- replikace viru účinky léků MeSH
- virové plášťové proteiny * antagonisté a inhibitory účinky léků MeSH
- Check Tag
- lidé MeSH
The synthesis of a novel library of purine derivatives bearing various bicyclic and polycylic substituents at the N-9 position is described. The series includes norbornanes, bicyclo[2.2.2]octanes, and bicyclo[3.2.1]octanes attached at the bridgehead position as well as bicyclo[3.1.1]heptanes, tetrahydro-1-naphthalenes, and adamantanes bonded either directly or via a linear chain to the 6-chloropurine nucleobase. A number of prepared derivatives exerted significant activity against the enterovirus. Despite attempts to correlate the activity against picornaviruses with their phosphatidylinositol 4-kinase KIIIβ inhibitory activity, it is clear that the inhibition of this host factor cannot explain the observed antiviral potency.
- MeSH
- antivirové látky chemická syntéza chemie farmakologie toxicita MeSH
- cytopatogenní efekt virový MeSH
- Enterovirus účinky léků fyziologie MeSH
- kultivované buňky MeSH
- molekulární struktura MeSH
- norbornany chemická syntéza chemie farmakologie toxicita MeSH
- přemostěné cyklické sloučeniny chemická syntéza chemie farmakologie toxicita MeSH
- puriny chemická syntéza chemie farmakologie toxicita MeSH
- replikace viru účinky léků MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Coxsackievirus and related enteroviruses are important human pathogens that cause various diseases with clinical manifestations ranging from trivial flu-like syndromes to dangerous or even fatal diseases such as myocarditis, meningitis and encephalitis. Here, we report on our continuous SAR study focused on 9-(bicyclo[2.2.1]hept-2-yl)-9H-purines as anti-enteroviral inhibitors. The purine moiety was modified at positions 2, 6 and 8. Several analogues inhibited Coxsackievirus B3 as well as other enteroviruses at low-micromolar concentrations. The 6-chloropurine derivative was confirmed as the most active compound in this series.
- MeSH
- antivirové látky chemická syntéza chemie farmakologie MeSH
- Cercopithecus aethiops MeSH
- Enterovirus účinky léků MeSH
- puriny chemická syntéza chemie farmakologie MeSH
- Vero buňky MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
(1R*,2R*,3R*,4S*)-7-Oxabicyclo[2.2.1]hept-5-ene-2,3-dimethanol (10) and (1R*,2R*,3R*,4S*)-bicyclo[2.2.2]oct-5-ene-2,3-dimethanol (14), which were prepared by the Diels–Alder reaction and subsequent reduction with lithium aluminium hydride, were treated with benzyl azidoformate to give benzyl N-[(1R*,2R*,3S*,6S*,7S*,9S*)-9-(hydroxymethyl)-4,8-dioxatricyclo[4.2.1.03,7]nonan-2-yl]carbamate (11) and benzyl N-[(1R*,2R*,3R*,6R*,7S*,10S*)-10-(hydroxymethyl)-4-oxatricyclo[4.3.1.03,7]decan-2-yl]carbamate (15). Hydrogenolysis of carbamates 11 or 15 afforded (1R*,2R*,3S*,6S*,7S*,9S*)-2-amino-4,8-dioxatricyclo[4.2.1.03,7]nonane-9-methanol (12) or (1R*,2R*,3R*,6R*,7S*,10S*)-2-amino-4-oxatricyclo[4.3.1.03,7]decane-10-methanol (16). The amines 12 and 16 were transformed to thymine and purine nucleoside analogues. The target compounds were tested for the activity against Coxsackie virus.
Hydroboration of [(1R*,2R*,4R*)-7-oxabicyclo[2.2.1]hept-5-en-2-yl]methyl benzoate (5), which was prepared by Diels–Alder reaction of furan with acrolein and subsequent reduction and benzoylation of the Diels–Alder product, afforded [(1R*,2S*,4S*,6S*)-6-hydroxy-7-oxabicyclo[2.2.1]heptan-2-yl]methyl benzoate (6) and [(1R*,2R*,4R*,5S*)-5-hydroxy-7-oxabicyclo[2.2.1]heptan-2-yl]methyl benzoate (7). The key intermediates, [(1R*,2S*,4S*,6R*)-6-hydroxy-7-oxabicyclo[2.2.1]heptan-2-yl]methyl benzoate (10) and [(1R*,2R*,4R*,5R*)-5-hydroxy-7-oxabicyclo[2.2.1]heptan-2-yl]methyl benzoate (11), were prepared from 6 and 7, respectively, by oxidation with pyridinium dichromate and subsequent reduction of the thus obtained ketones. The Mitsunobu reaction of 10 and 11 with 6-chloropurine and subsequent reductive deprotection with diisobutylaluminium hydride afforded 6-chloropurine derivatives, which were converted to other purine analogues. Thymine analogues were prepared by Mitsunobu reaction of 10 and 11 with 3-benzoyl-5-methylpyrimidine-2,4(1H,3H)-dione and subsequent methanolysis. The target compounds were tested for the activity against Coxsackie virus.
