The flavivirus, tick-borne encephalitis virus (TBEV) is transmitted by Ixodes spp. ticks and may cause severe and potentially lethal neurological tick-borne encephalitis (TBE) in humans. Studying TBEV requires the use of secondary methodologies to detect the virus in infected cells. To overcome this problem, we rationally designed and constructed a recombinant reporter TBEV that stably expressed the mCherry reporter protein. The resulting TBEV reporter virus (named mCherry-TBEV) and wild-type parental TBEV exhibited similar growth kinetics in cultured cells; however, the mCherry-TBEV virus produced smaller plaques. The magnitude of mCherry expression correlated well with progeny virus production but remained stable over <4 passages in cell culture. Using well-characterized antiviral compounds known to inhibit TBEV, 2'-C-methyladenosine and 2'-deoxy-2'-β-hydroxy-4'-azidocytidine (RO-9187), we demonstrated that mCherry-TBEV is suitable for high-throughput screening of antiviral drugs. Serum samples from a TBEV-vaccinated human and a TBEV-infected dog were used to evaluate the mCherry-based neutralization test. Collectively, recombinant mCherry-TBEV reporter virus described here provides a powerful tool to facilitate the identification of potential antiviral agents, and to measure levels of neutralizing antibodies in human and animal sera.
- MeSH
- antivirové látky izolace a purifikace MeSH
- buněčné linie MeSH
- klíšťová encefalitida imunologie virologie MeSH
- křečci praví MeSH
- ledviny cytologie MeSH
- lidé MeSH
- luminescentní proteiny genetika MeSH
- neutralizační testy * MeSH
- neutralizující protilátky krev MeSH
- protilátky virové krev MeSH
- rychlé screeningové testy metody MeSH
- viry klíšťové encefalitidy genetika růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS)-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC50 values of 0.92 and 1.43 µg∙mL(-1), respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC50 value of 82.4 µg∙mL(-1). This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.
- MeSH
- acyklovir farmakologie MeSH
- antivirové látky chemie izolace a purifikace farmakologie MeSH
- Cercopithecus aethiops MeSH
- Hibiscus chemie MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- inhibiční koncentrace 50 MeSH
- inhibitory enzymů chemie izolace a purifikace farmakologie MeSH
- kinetika MeSH
- lidský herpesvirus 2 účinky léků MeSH
- polyfenoly chemie izolace a purifikace farmakologie MeSH
- preklinické hodnocení léčiv MeSH
- rostlinné extrakty chemie izolace a purifikace farmakologie MeSH
- ureasa antagonisté a inhibitory chemie MeSH
- Vero buňky MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
There is growing evidence that Zika virus (ZIKV) can cause devastating infant brain defects and other neurological disorders in humans. However, no specific antiviral therapy is available at present. We tested a series of 2'-C- or 2'-O-methyl-substituted nucleosides, 2'-C-fluoro-2'-C-methyl-substituted nucleosides, 3'-O-methyl-substituted nucleosides, 3'-deoxynucleosides, derivatives with 4'-C-azido substitution, heterobase-modified nucleosides, and neplanocins for their ability to inhibit ZIKV replication in cell culture. Antiviral activity was identified when 2'-C-methylated nucleosides were tested, suggesting that these compounds might represent promising lead candidates for further development of specific antivirals against ZIKV.
- MeSH
- antivirové látky chemie izolace a purifikace farmakologie MeSH
- Cercopithecus aethiops MeSH
- mikrobiální testy citlivosti MeSH
- nukleosidy chemie izolace a purifikace farmakologie MeSH
- replikace viru účinky léků MeSH
- Vero buňky MeSH
- virus zika účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: In this review, we highlight and summarise the most promising extracts, fractions and pure compounds as potential anti-herpes simplex virus (HSV) agents derived from microorganisms, marine organisms, fungi, animals and plants. The role of natural products in the development of anti-HSV drugs will be discussed. KEY FINDINGS: Herpes simplex viruses (HSV-1 and -2) are common human pathogens that remain a serious threat to human health. In recent years, a great interest has been devoted to the search for integrated management of HSV infections. Acyclovir and related nucleoside analogues have been licensed for the therapy that target viral DNA polymerase. Although these drugs are currently effective against HSV infections, the intensive use of these drugs has led to the problem of drug-resistant strains. Therefore, the search for new sources to develop new antiherpetic agents has gained major priority to overcome the problem. SUMMARY: Natural products as potential, new anti-HSV drugs provide several advantages such as reduced side effects, less resistance, low toxicity and various mechanisms of action. This paper aims to provide an overview of natural products that possess antiviral activity against HSV.
- MeSH
- antivirové látky škodlivé účinky izolace a purifikace farmakologie MeSH
- biologické přípravky škodlivé účinky izolace a purifikace farmakologie MeSH
- herpes simplex farmakoterapie virologie MeSH
- lidé MeSH
- lidský herpesvirus 1 izolace a purifikace MeSH
- racionální návrh léčiv MeSH
- virová léková rezistence MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- alkaloidy * izolace a purifikace terapeutické užití MeSH
- antiretrovirové látky izolace a purifikace MeSH
- antivirové látky * izolace a purifikace MeSH
- diarylheptanoidy chemie izolace a purifikace terapeutické užití MeSH
- Hepacivirus účinky léků MeSH
- látky proti HIV izolace a purifikace MeSH
- léčivé rostliny chemie imunologie MeSH
- rostlinné extrakty terapeutické užití MeSH
- T-lymfocyty pomocné-indukující účinky léků MeSH
- toll-like receptory účinky léků MeSH
- virus hepatitidy B účinky léků MeSH
- MeSH
- antivirové látky * izolace a purifikace MeSH
- benzofurany farmakologie izolace a purifikace terapeutické užití MeSH
- flavonoidy farmakologie izolace a purifikace terapeutické užití MeSH
- látky proti HIV farmakologie izolace a purifikace terapeutické užití MeSH
- léčivé rostliny chemie MeSH
- lišejníky chemie MeSH
- listy rostlin chemie MeSH
- oleje rostlin farmakologie izolace a purifikace terapeutické užití MeSH
- polyfenoly farmakologie izolace a purifikace terapeutické užití MeSH
- polysacharidy farmakologie izolace a purifikace terapeutické užití MeSH
- rostlinné extrakty * terapeutické užití MeSH
- sinice chemie MeSH
- terpeny farmakologie izolace a purifikace terapeutické užití MeSH
Expression of the previously reported defensin of the tick Dermacentor marginatus (defDM) was analysed in different organs by RT-PCR. mRNA of the defDM gene was detected in the hemolymph, midgut and salivary glands. Moreover defDM was isolated from the tick hemolymph using RP-HPLC and its sequence was determined by mass spectrometry and Edman degradation. Synthetic peptide was used for determining biological activities. The results showed an anti-Gram-positive bacterial role for the defensin. As D. marginatus ticks appear not to be vectors of the Lyme disease agent of the complex Borrelia burgdorferi sensu lato, we tested the influence of defDM on Borrelia afzelii. There is a very clear borrelicidal activity of the defensin, which is concentration dependent and suggests a possible role in the clearing of Borrelia ingested by D. marginatus ticks.
- MeSH
- antibakteriální látky izolace a purifikace farmakologie MeSH
- antifungální látky izolace a purifikace farmakologie MeSH
- antivirové látky izolace a purifikace farmakologie MeSH
- Borrelia burgdorferi komplex účinky léků MeSH
- defensiny izolace a purifikace farmakologie MeSH
- Dermacentor chemie MeSH
- mikrobiální testy citlivosti MeSH
- proteiny členovců izolace a purifikace farmakologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
