Anti-Hepatitis C virus activity of uridine derivatives of 2-deoxy sugars

Ewelina Król , Ilona Wandzik , Gabriela Pastuch-Gawołek , Bogusław Szewczyk

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.
Author Ewelina Król (IFB / IB / LRV)
Ewelina Król,,
- Laboratory of Recombinant Vaccines
, Ilona Wandzik
Ilona Wandzik,,
-
, Gabriela Pastuch-Gawołek
Gabriela Pastuch-Gawołek,,
-
, Bogusław Szewczyk (IFB / IB / LRV)
Bogusław Szewczyk,,
- Laboratory of Recombinant Vaccines
Journal seriesMolecules, ISSN 1420-3049, (A 30 pkt)
Issue year2018
Vol23
No7
Pages1-18
Keywords in Englishhepatitis C virus, antiviral compounds, uridine, 2-deoxy sugars, glycosylation inhibition
ASJC Classification1605 Organic Chemistry
DOIDOI:10.3390/molecules23071547
URL https://www.mdpi.com/1420-3049/23/7/1547/pdf
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)30
Score sourcejournalList
ScoreMinisterial score = 30.0, 17-11-2019, ArticleFromJournal
Publication indicators WoS Citations = 0; 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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