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

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, the...

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Autores principales: Krol, Ewelina, Wandzik, Ilona, Brzuska, Gabriela, Eyer, Luděk, Růžek, Daniel, Szewczyk, Boguslaw
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471225/
https://www.ncbi.nlm.nih.gov/pubmed/30901934
http://dx.doi.org/10.3390/molecules24061129
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author Krol, Ewelina
Wandzik, Ilona
Brzuska, Gabriela
Eyer, Luděk
Růžek, Daniel
Szewczyk, Boguslaw
author_facet Krol, Ewelina
Wandzik, Ilona
Brzuska, Gabriela
Eyer, Luděk
Růžek, Daniel
Szewczyk, Boguslaw
author_sort Krol, Ewelina
collection PubMed
description 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 IC(50) 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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spelling pubmed-64712252019-04-26 Antiviral Activity of Uridine Derivatives of 2-Deoxy Sugars against Tick-Borne Encephalitis Virus Krol, Ewelina Wandzik, Ilona Brzuska, Gabriela Eyer, Luděk Růžek, Daniel Szewczyk, Boguslaw Molecules Article 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 IC(50) 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. MDPI 2019-03-21 /pmc/articles/PMC6471225/ /pubmed/30901934 http://dx.doi.org/10.3390/molecules24061129 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Krol, Ewelina
Wandzik, Ilona
Brzuska, Gabriela
Eyer, Luděk
Růžek, Daniel
Szewczyk, Boguslaw
Antiviral Activity of Uridine Derivatives of 2-Deoxy Sugars against Tick-Borne Encephalitis Virus
title Antiviral Activity of Uridine Derivatives of 2-Deoxy Sugars against Tick-Borne Encephalitis Virus
title_full Antiviral Activity of Uridine Derivatives of 2-Deoxy Sugars against Tick-Borne Encephalitis Virus
title_fullStr Antiviral Activity of Uridine Derivatives of 2-Deoxy Sugars against Tick-Borne Encephalitis Virus
title_full_unstemmed Antiviral Activity of Uridine Derivatives of 2-Deoxy Sugars against Tick-Borne Encephalitis Virus
title_short Antiviral Activity of Uridine Derivatives of 2-Deoxy Sugars against Tick-Borne Encephalitis Virus
title_sort antiviral activity of uridine derivatives of 2-deoxy sugars against tick-borne encephalitis virus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471225/
https://www.ncbi.nlm.nih.gov/pubmed/30901934
http://dx.doi.org/10.3390/molecules24061129
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