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Molecules 2018, 23(7), 1547; https://doi.org/10.3390/molecules23071547

Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars

1
Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland
2
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland
3
Biotechnology Center, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Christian Ducho
Received: 24 May 2018 / Revised: 22 June 2018 / Accepted: 26 June 2018 / Published: 27 June 2018
(This article belongs to the Special Issue Bioactive Nucleosides and Nucleotides)
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Abstract

Hepatitis C virus (HCV), the etiological agent of the most common and dangerous diseases of the liver, is a major health problem worldwide. Despite many attempts, there is still no vaccine available. Although many drugs have been approved for use mostly in combination regimen, their high costs make them out of reach in less developed regions. Previously, we have synthesized a series of compounds belonging to uridine derivatives of 2-deoxy sugars and have proved that some of them possess antiviral activity against influenza A virus associated with N-glycosylation inhibition. Here, we analyze the antiviral properties of these compounds against HCV. Using cell culture-derived HCV (HCVcc), HCV pseudoparticles (HCVpp), and replicon cell lines, we have shown high anti-HCV activity of two compounds. Our results indicated that compounds 2 and 4 significantly reduced HCVcc propagation with IC50 values in low μM range. Further experiments using the HCVpp system confirmed that both compounds significantly impaired the infectivity of produced HCVpp due to the inhibition of the correct maturation of viral glycoproteins. Overall, our results suggest that inhibiting the glycosylation process might be a good target for new therapeutics not only against HCV, but other important viral pathogens which contain envelopes with highly glycosylated proteins. View Full-Text
Keywords: hepatitis C virus; antiviral compounds; uridine; 2-deoxy sugars; glycosylation inhibition hepatitis C virus; antiviral compounds; uridine; 2-deoxy sugars; glycosylation inhibition
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Krol, E.; Wandzik, I.; Pastuch-Gawolek, G.; Szewczyk, B. Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars. Molecules 2018, 23, 1547.

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