Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Krol, Ewelina, Wandzik, Ilona, Pastuch-Gawolek, Gabriela, Szewczyk, Boguslaw
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099588/
https://www.ncbi.nlm.nih.gov/pubmed/29954068
http://dx.doi.org/10.3390/molecules23071547
_version_ 1783348700121137152
author Krol, Ewelina
Wandzik, Ilona
Pastuch-Gawolek, Gabriela
Szewczyk, Boguslaw
author_facet Krol, Ewelina
Wandzik, Ilona
Pastuch-Gawolek, Gabriela
Szewczyk, Boguslaw
author_sort Krol, Ewelina
collection PubMed
description 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 IC(50) 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.
format Online
Article
Text
id pubmed-6099588
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-60995882018-11-13 Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars Krol, Ewelina Wandzik, Ilona Pastuch-Gawolek, Gabriela Szewczyk, Boguslaw Molecules Article 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 IC(50) 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. MDPI 2018-06-27 /pmc/articles/PMC6099588/ /pubmed/29954068 http://dx.doi.org/10.3390/molecules23071547 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Krol, Ewelina
Wandzik, Ilona
Pastuch-Gawolek, Gabriela
Szewczyk, Boguslaw
Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars
title Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars
title_full Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars
title_fullStr Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars
title_full_unstemmed Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars
title_short Anti-Hepatitis C Virus Activity of Uridine Derivatives of 2-Deoxy Sugars
title_sort anti-hepatitis c virus activity of uridine derivatives of 2-deoxy sugars
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099588/
https://www.ncbi.nlm.nih.gov/pubmed/29954068
http://dx.doi.org/10.3390/molecules23071547
work_keys_str_mv AT krolewelina antihepatitiscvirusactivityofuridinederivativesof2deoxysugars
AT wandzikilona antihepatitiscvirusactivityofuridinederivativesof2deoxysugars
AT pastuchgawolekgabriela antihepatitiscvirusactivityofuridinederivativesof2deoxysugars
AT szewczykboguslaw antihepatitiscvirusactivityofuridinederivativesof2deoxysugars