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Molecules, Vol. 23, Pages 1547: Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars

Molecules, Vol. 23, Pages 1547: Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars

Molecules doi: 10.3390/molecules23071547

Authors: Ewelina Krol Ilona Wandzik Gabriela Pastuch-Gawolek Boguslaw Szewczyk

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.

Authors:   Krol, Ewelina ; Wandzik, Ilona ; Pastuch-Gawolek, Gabriela ; Szewczyk, Boguslaw
Journal:   Molecules
Volume:   23
edition:   7
Year:   2018
Pages:   1547
DOI:   10.3390/molecules23071547
Publication date:   27-Jun-2018
Facts, background information, dossiers
  • Uridine
  • therapeutics
  • sugars
  • liver
  • influenza
  • infectivity
  • glycoproteins
  • drugs
  • diseases
  • cell lines
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