Biological evaluation of uridine derivatives of 2-deoxy sugars as potential antiviral compounds against influenza A virus

Ewelina Król , Ilona Wandzik , Martyna Krejmer-Rąbalska , Bogusław Szewczyk


Influenza virus infection is a major cause of morbidity and mortality worldwide. Due to the limited ability of currently available treatments, there is an urgent need for new anti-influenza drugs with broad spectrum protection. We have previously shown that two 2-deoxy sugar derivatives of uridine (designated IW3 and IW7) targeting the glycan processing steps during maturation of viral glycoproteins show good anti-influenza virus activity and may be a promising alternative approach for the development of new anti-influenza therapy. In this study, a number of IW3 and IW7 analogues with different structural modifications in 2-deoxy sugar or uridine parts were synthesized and evaluated for their ability to inhibit influenza A virus infection in vitro. Using the cytopathic effect (CPE) inhibition assay and viral plaque reduction assay in vitro, we showed that compounds 2, 3, and 4 exerted the most inhibitory effect on influenza virus A/ostrich/Denmark/725/96 (H5N2) infection in Madin-Darby canine kidney (MDCK) cells, with 50% inhibitory concentrations (IC50) for virus growth ranging from 82 to 100 (μM) without significant toxicity for the cells. The most active compound (2) showed activity of 82 μM with a selectivity index value of 5.27 against type A (H5N2) virus. Additionally, compound 2 reduced the formation of HA glycoprotein in a dose-dependent manner. Moreover, an analysis of physicochemical properties of studied compounds demonstrated a significant linear correlation between lipophilicity and antiviral activity. Therefore, inhibition of influenza A virus infection by conjugates of uridine and 2-deoxy sugars is a new promising approach for the development of new derivatives with anti-influenza activities.
Author Ewelina Król (IFB/IB/LRV)
Ewelina Król,,
- Laboratory of Recombinant Vaccines
, Ilona Wandzik
Ilona Wandzik,,
, Martyna Krejmer-Rąbalska (IFB)
Martyna Krejmer-Rąbalska,,
- Intercollegiate Faculty of Biotechnology UG
, Bogusław Szewczyk (IFB/IB/LRV)
Bogusław Szewczyk,,
- Laboratory of Recombinant Vaccines
Journal seriesInternational Journal of Molecular Sciences, ISSN 1661-6596, e-ISSN 1422-0067, (A 30 pkt)
Issue year2017
Publication size in sheets0.65
Article number1700
Keywords in Englishinfluenza A virus, antiviral compounds, uridine, 2-deoxy sugars, glycosylation inhibition
ASJC Classification2700 General Medicine; 1312 Molecular Biology; 1503 Catalysis; 1604 Inorganic Chemistry; 1605 Organic Chemistry; 1606 Physical and Theoretical Chemistry; 1607 Spectroscopy; 1706 Computer Science Applications
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)30
Score sourcejournalList
ScoreMinisterial score = 30.0, 03-02-2020, ArticleFromJournal
Publication indicators WoS Citations = 2.000; Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.151; WoS Impact Factor: 2017 = 3.687 (2) - 2017=3.878 (5)
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