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.

Biotechnology Center Silesian University of Technology Krzywoustego 8 44 100 Gliwice Poland

Department of Organic Chemistry Bioorganic Chemistry and Biotechnology Faculty of Chemistry Silesian University of Technology Krzywoustego 4 44 100 Gliwice Poland

Department of Recombinant Vaccines Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk Abrahama 58 80 307 Gdansk Poland

Department of Virology Veterinary Research Institute Hudcova 70 CZ 62100 Brno Czech Republic

Institute of Parasitology Biology Centre of the Czech Academy of Sciences Branisovska 31 CZ 37005 Ceske Budejovice Czech Republic

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History of Arbovirus Research in the Czech Republic