scholarly journals Anti-Tick-Borne Encephalitis Virus Activity of Novel Uridine Glycoconjugates Containing Amide or/and 1,2,3-Triazole Moiety in the Linker Structure

2020 ◽  
Vol 13 (12) ◽  
pp. 460
Author(s):  
Gabriela Brzuska ◽  
Gabriela Pastuch-Gawolek ◽  
Monika Krawczyk ◽  
Boguslaw Szewczyk ◽  
Ewelina Krol
Keyword(s):  
Antiviral Treatment ◽  
Encephalitis Virus ◽  
In Vitro Assays ◽  
Strong Activity ◽  
Tick Borne Encephalitis ◽  
Ic50 Values ◽  
Low Cytotoxicity ◽  
Tick Borne Encephalitis Virus ◽  
Further Development

Tick-borne encephalitis virus (TBEV) transmitted by ticks is a pathogen of great medical importance. As still no effective antiviral treatment is available, in the present study, a series of uridine glycoconjugates containing amide or/and 1,2,3-triazole moiety in the linker structure was synthesized and evaluated for the antiviral activity against two strains of TBEV: a highly virulent Hypr strain and less virulent Neudoerfl strain, using standardized previously in vitro assays. Our data have shown that four compounds from the series (18–21) possess strong activity against both TBEV strains. The half maximal inhibitory concentration (IC50) values of compounds 18–21 were between 15.1 and 3.7 μM depending on the virus strain, which along with low cytotoxicity resulted in high values of the selectivity index (SI). The obtained results suggest that these compounds may be promising candidates for further development of new therapies against flaviviruses.

scholarly journals Tick-Borne Encephalitis Virus: A Quest for Better Vaccines against a Virus on the Rise

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 451 ◽  
Author(s):  
Mareike Kubinski ◽  
Jana Beicht ◽  
Thomas Gerlach ◽  
Asisa Volz ◽  
Gerd Sutter ◽  
...  
Keyword(s):  
Antiviral Treatment ◽  
Encephalitis Virus ◽  
Protective Measure ◽  
Humoral And Cellular Immunity ◽  
Tick Borne Encephalitis ◽  
The Family ◽  
The Central Nervous System ◽  
Tick Borne Encephalitis Virus ◽  
Protection Against Infection ◽  
Vaccine Failures

Tick-borne encephalitis virus (TBEV), a member of the family Flaviviridae, is one of the most important tick-transmitted viruses in Europe and Asia. Being a neurotropic virus, TBEV causes infection of the central nervous system, leading to various (permanent) neurological disorders summarized as tick-borne encephalitis (TBE). The incidence of TBE cases has increased due to the expansion of TBEV and its vectors. Since antiviral treatment is lacking, vaccination against TBEV is the most important protective measure. However, vaccination coverage is relatively low and immunogenicity of the currently available vaccines is limited, which may account for the vaccine failures that are observed. Understanding the TBEV-specific correlates of protection is of pivotal importance for developing novel and improved TBEV vaccines. For affording robust protection against infection and development of TBE, vaccines should induce both humoral and cellular immunity. In this review, the adaptive immunity induced upon TBEV infection and vaccination as well as novel approaches to produce improved TBEV vaccines are discussed.

scholarly journals Spectrum of antiviral activity of 4-aminopyrimidine N-oxides against a broad panel of tick-borne encephalitis virus strains

2020 ◽  
Vol 28 ◽  
pp. 204020662094346
Author(s):  
Evgenia V Dueva ◽  
Ksenia K Tuchynskaya ◽  
Liubov I Kozlovskaya ◽  
Dmitry I Osolodkin ◽  
Kseniya N Sedenkova ◽  
...  
Keyword(s):  
Encephalitis Virus ◽  
Northern Eurasia ◽  
Virus Particles ◽  
E Protein ◽  
Tick Borne Encephalitis ◽  
Tbev Strain ◽  
Amino Phenol ◽  
Tick Borne Encephalitis Virus ◽  
Immature Virus

Tick-borne encephalitis is an important human arbovirus neuroinfection spread across the Northern Eurasia. Inhibitors of tick-borne encephalitis virus (TBEV) strain Absettarov, presumably targeting E protein n-octyl-β-d-glucoside (β-OG) pocket, were reported earlier. In this work, these inhibitors were tested in vitro against seven strains representing three main TBEV subtypes. The most potent compound, 2-[(2-methyl-1-oxido-5,6,7,8-tetrahydroquinazolin-4-yl)amino]-phenol, showed EC50 values lower than 22 µM against all the tested strains. Nevertheless, EC50 values for virus samples of certain strains demonstrated a substantial variation, which appeared to be consistent with the presence of E protein not only in infectious virions, but also in non-infectious and immature virus particles, protein aggregates, and membrane complexes.

scholarly journals Antiviral Properties of Water Extracts of Mycelium Inonotus rheades (Pers.) P. Karst. (1882) against the Virus of Tick-Borne Encephalitis Virus in vitro

2021 ◽  
Vol 6 (1) ◽  
pp. 55-59
Author(s):  
M. A. Khasnatinov ◽  
T. G. Gornostai ◽  
I. S. Solovarov ◽  
M. S. Polyakova ◽  
G. A. Danchinova ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Antiviral Agents ◽  
Encephalitis Virus ◽  
Water Soluble ◽  
Xylotrophic Basidiomycetes ◽  
Tick Borne Encephalitis ◽  
Wood Polysaccharides ◽  
Tick Borne Encephalitis Virus ◽  
The Relationship

Background. Tick-borne encephalitis virus is dangerous and widespread pathogen that is transmitted to humans through the bites of hard ticks. Wild fungi, such as xylotrophic basidiomycetes, are widely used in traditional medicine to treat the infectious diseases and are promising natural sources of new antiviral agents. It was previously shown that aqueous extracts from the mycelium of the Inonotus rheades (Pers.) P. Karst. (1882) fungus exhibit significant antiviral activity against tick-borne encephalitis virus, however, the mechanisms of this activity remain unclear.Aim. To analyze the relationship between the virucidal properties of I. rheades extract and the substrate on which the cultivation was carried out.Materials and methods. The mycelium was grown either in a standard liquid medium with wort or on wooden disks from birch. Extracts of water-soluble polysaccharides were prepared from both mycelium samples. The concentration of infectious tick-borne encephalitis virus was determined using the method of titration of plaque-forming components (PFU). Approximately 30 000 PFU of tick-borne encephalitis virus was mixed with an equal volume of corresponding I. rheades extract at concentration of 8 mg/mL and incubated for 30 min at 37 °C. Afterwards, the residual infectivity of tick-borne encephalitis virus was determined using the identical virus sample incubated with sterile water as a reference.Results. It was found that treatment of tick-borne encephalitis virus with extracts from I. rheades mycelium resulted in inhibition of the infectivity of the virus in the cell culture. However, the same strain of I. rheades, grown on medium with wort, did not exhibit antiviral properties.Conclusions. Virucidal substances are likely to be not the main metabolites of the mycelium of I. rheades, but are rather metabolized wood polysaccharides. Further research is needed to more accurately identify the active ingredients and assess their antiviral activity.

scholarly journals Tick-Borne Encephalitis Virus Vaccine-Induced Human Antibodies Mediate Negligible Enhancement of Zika Virus Infection In Vitro and in a Mouse Model

mSphere ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
James Duehr ◽  
Silviana Lee ◽  
Gursewak Singh ◽  
Gregory A. Foster ◽  
David Krysztof ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dengue Virus ◽  
Human Plasma ◽  
Mouse Models ◽  
Zika Virus ◽  
Encephalitis Virus ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

ABSTRACT Recent reports in the scientific literature have suggested that anti-dengue virus (DENV) and anti-West Nile virus (WNV) immunity exacerbates Zika virus (ZIKV) pathogenesis in vitro and in vivo in mouse models. Large populations of immune individuals exist for a related flavivirus (tick-borne encephalitis virus [TBEV]), due to large-scale vaccination campaigns and endemic circulation throughout most of northern Europe and the southern Russian Federation. As a result, the question of whether anti-TBEV immunity can affect Zika virus pathogenesis is a pertinent one. For this study, we obtained 50 serum samples from individuals vaccinated with the TBEV vaccine FSME-IMMUN (Central European/Neudörfl strain) and evaluated their enhancement capacity in vitro using K562 human myeloid cells expressing CD32 and in vivo using a mouse model of ZIKV pathogenesis. Among the 50 TBEV vaccinee samples evaluated, 29 had detectable reactivity against ZIKV envelope (E) protein by enzyme-linked immunosorbent assay (ELISA), and 36 showed enhancement of ZIKV infection in vitro. A pool of the most highly reacting and enhanced samples resulted in no significant change in the morbidity/mortality of ZIKV disease in immunocompromised Stat2−/− mice. Our results suggest that humoral immunity against TBEV is unlikely to enhance Zika virus pathogenesis in humans. No clinical reports indicating that TBEV vaccinees experiencing enhanced ZIKV disease have been published so far, and though the epidemiological data are sparse, our findings suggest that there is little reason for concern. This study also displays a clear relationship between the phylogenetic distance between two flaviviruses and their capacity for pathogenic enhancement. IMPORTANCE The relationship between serial infections of two different serotypes of dengue virus and more severe disease courses is well-documented in the literature, driven by so-called antibody-dependent enhancement (ADE). Recently, studies have shown the possibility of ADE in cells exposed to anti-DENV human plasma and then infected with ZIKV and also in mouse models of ZIKV pathogenesis after passive transfer of anti-DENV human plasma. In this study, we evaluated the extent to which this phenomenon occurs using sera from individuals immunized against tick-borne encephalitis virus (TBEV). This is highly relevant, since large proportions of the European population are vaccinated against TBEV or otherwise seropositive.

scholarly journals Characterization and in vitro assembly of tick‐borne encephalitis virus C protein

FEBS Letters ◽  
2020 ◽  
Vol 594 (12) ◽  
pp. 1989-2004
Author(s):  
Filip Kaufman ◽  
Alžběta Dostálková ◽  
Lukáš Pekárek ◽  
Tung Dinh Thanh ◽  
Marina Kapisheva ◽  
...  
Keyword(s):  
Encephalitis Virus ◽  
C Protein ◽  
Tick Borne Encephalitis ◽  
In Vitro Assembly ◽  
Tick Borne Encephalitis Virus ◽  
Virus C

scholarly journals RNA interference inhibits replication of tick-borne encephalitis virus in vitro

2012 ◽  
Vol 93 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Katharina Achazi ◽  
Pranav Patel ◽  
Ravish Paliwal ◽  
Aleksandar Radonić ◽  
Matthias Niedrig ◽  
...  
Keyword(s):  
Rna Interference ◽  
Encephalitis Virus ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

scholarly journals Comprehensive assessment of specific antibodies on infectious activity of tick-borne encephalitis virus

2019 ◽  
Vol 9 (3-4) ◽  
pp. 559-567
Author(s):  
G. N. Leonova ◽  
O. S. Majstrovskaya ◽  
V. A. Lubova ◽  
N. B. Sanina
Keyword(s):  
Ex Vivo ◽  
Experimental Studies ◽  
Encephalitis Virus ◽  
Virus Elimination ◽  
Specific Antibodies ◽  
Tick Borne Encephalitis ◽  
Antibody Titers ◽  
Tick Borne Encephalitis Virus

Vaccines for prophylactic immunization provide the most reliable and effective protection against the vast majority of infectious diseases. Tick-borne encephalitis (TBE) represents a high-priority medical issue at the territory of the Eurasian continent. Of great importance is assessing a role of distinct antibody titers especially low titers, observed quite often in vaccinated individuals, sometimes posing obstacles in determining a threshold of seropositivity as well as the level of specific protection against TBE virus. We aimed at obtaining data to assess antiviral activity of virus-specific antibodies with distinct titer levels based on the in vitro, ex vivo and in vivo experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus. The in vitro, ex vivo and in vivo comprehensive experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus (TBEV) were conducted and the dynamics of antiviral activity of virus-specific antibodies at variable titers (1:100–1:3200) was measured (timeframe ranged within 1–96 hours p.i.) to provide a rationale for evaluating the antiviral immune response. It was found that the in vitro experiments demonstrated that the IgG at 1:100 titer exerted a weak anti-TBEV neutralizing effect at all time-points examined. The IgG 1:400 titer caused a 2 log PFU/mL decline in TBEV Dal strain yield at 72 h post-infection, whereas at 1:3200 titer it completely suppressed TBEV replication throughout the observation period. The ex vivo experiments with blood serum obtained from vaccinated subjects demonstrating a range of TBEV antibody titers (sera from vaccinated individuals with varying anti-TBEV antibody titers) and in vivo (outinbred white mice) experiments revealed a delayed virus elimination for antibody titers at 1:100 and 1:200 as well as rapid virus elimination (1–2 days p.i.) for antibody titers greater than 1:400. Thus, antibody titer at 1:400 may be considered as the universal anti-TBEV protection threshold. In order to properly conclude regarding the revaccination schedule it is advised to start with testing blood serum for durability of anti-TBEV immune response. Subjects with TBEV antibody titers at 1:100 and 1:200 should be strongly recommended to undergo a mandatory revaccination. Such an approach is believed to be the most effective way toward enhancing efficacy of vaccine-mediated protection against TBE.

Translation of tick-borne encephalitis virus (flavivirus) genome in vitro: Synthesis of two structural polypeptides

Virology ◽  
1981 ◽  
Vol 110 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Y.V. Svitkin ◽  
T.Y. Ugarova ◽  
T.V. Chernovskaya ◽  
V.N. Lyapustin ◽  
V.A. Lashkevich ◽  
...  
Keyword(s):  
Encephalitis Virus ◽  
In Vitro Synthesis ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

scholarly journals Antiviral Activity of Uridine Derivatives of 2-Deoxy Sugars against Tick-Borne Encephalitis Virus

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1129 ◽  
Author(s):  
Ewelina Krol ◽  
Ilona Wandzik ◽  
Gabriela Brzuska ◽  
Luděk Eyer ◽  
Daniel Růžek ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Virulent Strain ◽  
Encephalitis Virus ◽  
Antiviral Therapies ◽  
Tick Borne Encephalitis ◽  
Tbev Strain ◽  
Ic50 Values ◽  
Tick Borne Encephalitis Virus ◽  
Derivatives Of ◽  
Deoxy Sugars

Tick-borne encephalitis virus (TBEV) is a causative agent of tick-borne encephalitis (TBE), one of the most important human infections involving the central nervous system. Although effective vaccines are available on the market, they are recommended only in endemic areas. Despite many attempts, there are still no specific antiviral therapies for TBEV treatment. Previously, we synthesized a series of uridine derivatives of 2-deoxy sugars and proved that some compounds show antiviral activity against viruses from the Flaviviridae and Orthomyxoviridae families targeting the late steps of the N-glycosylation process, affecting the maturation of viral proteins. In this study, we evaluated a series of uridine derivatives of 2-deoxy sugars for their antiviral properties against two strains of the tick-borne encephalitis virus; the highly virulent TBEV strain Hypr and the less virulent strain Neudoerfl. Four compounds (2, 4, 10, and 11) showed significant anti-TBEV activity with IC50 values ranging from 1.4 to 10.2 µM and low cytotoxicity. The obtained results indicate that glycosylation inhibitors, which may interact with glycosylated membrane TBEV E and prM proteins, might be promising candidates for future antiviral therapies against TBEV.

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