Antiviral activity of uridine derivatives of 2-deoxy sugars against tick-borne encephalitis virus

Ewelina Król , Ilona Wandzik , Gabriela Brzuska , Luděk Eyer , Daniel Růžek , Bogusław Szewczyk

Abstract

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.
Author Ewelina Król (IFB / IB / LRV)
Ewelina Król,,
- Laboratory of Recombinant Vaccines
, Ilona Wandzik
Ilona Wandzik,,
-
, Gabriela Brzuska (IFB)
Gabriela Brzuska,,
- Intercollegiate Faculty of Biotechnology UG
, Luděk Eyer
Luděk Eyer,,
-
, Daniel Růžek
Daniel Růžek,,
-
, Bogusław Szewczyk (IFB / IB / LRV)
Bogusław Szewczyk,,
- Laboratory of Recombinant Vaccines
Journal seriesMolecules, ISSN 1420-3049, (N/A 100 pkt)
Issue year2019
Vol24
No6
Pages1-12
Publication size in sheets0.55
Article number1129
Keywords in Englishtick-borne encephalitis, antivirals, glycosylation inhibition, uridine, 2-deoxy sugars
ASJC Classification1605 Organic Chemistry
DOIDOI:10.3390/molecules24061129
URL https://doi.org/10.3390/molecules24061129
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 17-11-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.146; WoS Impact Factor: 2018 = 3.06 (2) - 2018=3.38 (5)
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