Novel thioglycosyl analogs of glycosyltransferase substrates as antiviral compounds against classical swine fever virus and hepatitis C virus

Pastuch-Gawołek, Gabriela; Chaubey, Binay; Szewczyk, Bogusław; Król, Ewelina

doi:10.1016/j.ejmech.2017.05.051

Cited by 16 publications

(19 citation statements)

References 39 publications

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“…To evaluate the anti-HCV activity of all compounds, Huh-7.5 cell culture-derived HCV (HCVcc), which allows for complete HCV life cycle in cell culture including in vitro production and secretion of HCVcc, was used [ 28 , 29 ]. Jc1/JFH genotype 2a infected Huh-7.5 cells were treated with 50 μM of inhibitors or DMSO and HCVcc pseudoplaque reduction assay was performed as the preliminary screening of compounds as previously described [ 30 ]. The antiviral activity was evaluated by the reduction of infected cells (pseudoplaques).…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2018

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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.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2018

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“…Since the formation of Ribavirin (RBV) and PEGylated interferon alpha (IFN-α) as the standard drugs for the medical treatment of HCV in 1990, large efforts have been made to find new and more effective drugs. New effective HCV inhibitors belonging to direct-acting antivirals (DAAs), which include Boceprevir, Ledipasvir, Sofosbuvir, Telaprevir, Simeprevir, and Daclatasvir, have been developed in recent years [ 71 ]. Although great progress in anti-HCV remedies has been surely attained, many barriers nevertheless exist.…”

Section: Phytochemical Studies and Anti-viral Activities Of Oamentioning

confidence: 99%

Antiviral Activities of Oleanolic Acid and Its Analogues

2018

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Viral diseases, such as human immune deficiency virus (HIV), influenza, hepatitis, and herpes, are the leading causes of human death in the world. The shortage of effective vaccines or therapeutics for the prevention and treatment of the numerous viral infections, and the great increase in the number of new drug-resistant viruses, indicate that there is a great need for the development of novel and potent antiviral drugs. Natural products are one of the most valuable sources for drug discovery. Most natural triterpenoids, such as oleanolic acid (OA), possess notable antiviral activity. Therefore, it is important to validate how plant isolates, such as OA and its analogues, can improve and produce potent drugs for the treatment of viral disease. This article reports a review of the analogues of oleanolic acid and their selected pathogenic antiviral activities, which include HIV, the influenza virus, hepatitis B and C viruses, and herpes viruses.

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“…Recently, we have reported the identification and mechanism of action of a series of glycoconjugates as anti-CSFV and -HCV compounds [ 27 , 28 ]. These were derivatives of (5-amino-2-pyridyl) 1-thioglycosides and selectively protected uridine, a new kind of sugar nucleotide analogue designed as a potential GT inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Novel Uridine Glycoconjugates, Derivatives of 4-Aminophenyl 1-Thioglycosides, as Potential Antiviral Compounds

et al. 2018

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A novel series of uridine glycoconjugates, derivatives of 4-aminophenyl 1-thioglycosides, was designed and synthesized. All compounds were evaluated in vitro for their antiviral activity against hepatitis C virus (HCV) and classical swine fever virus (CSFV), two important human and animal viral pathogens for which new or improved therapeutic options are needed. The antiviral activity of all synthesized compounds was confirmed using pseudo-plaque reduction assays in which a significant arrest of CSFV and HCV growth was observed in the presence of these compounds. Two of the synthesized compounds, 9 and 12, displayed a significant inhibitory effect on HCV and CSFV propagation with IC50 values of 4.9 and 13.5 µM for HCV and 4.2 and 4 µM for CSFV, respectively, with low cytotoxicity. Using various infection and replication models, we have shown that both compounds were able to significantly reduce viral genome replication by up to 90% with IC50 values in the low micromolar range. A structure activity analysis of the synthesized compounds showed that the high antiviral activity was attributed to the hydrophobicity of glycoconjugates and the introduction of elements capable to coordinate metal ions into the spacer connecting the sugar and uridine moiety, which can be useful in the development of new antiviral compounds in the future.

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Novel thioglycosyl analogs of glycosyltransferase substrates as antiviral compounds against classical swine fever virus and hepatitis C virus

Cited by 16 publications

References 39 publications

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

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

Antiviral Activities of Oleanolic Acid and Its Analogues

Novel Uridine Glycoconjugates, Derivatives of 4-Aminophenyl 1-Thioglycosides, as Potential Antiviral Compounds

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