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
AbstractTick-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.
|Journal series||Molecules, ISSN 1420-3049, (N/A 100 pkt)|
|Publication size in sheets||0.55|
|Keywords in English||tick-borne encephalitis, antivirals, glycosylation inhibition, uridine, 2-deoxy sugars|
|License||Journal (articles only); published final; ; with publication|
|Score||= 100.0, 17-11-2019, ArticleFromJournal|
|Publication indicators||: 2017 = 1.146; : 2018 = 3.06 (2) - 2018=3.38 (5)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.