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Inhibitory Effects of Novel Nucleoside and Nucleotide Analogues on Epstein—Barr Virus Replication:

Inhibitory Effects of Novel Nucleoside and Nucleotide Analogues on Epstein—Barr Virus Replication: The anti-Epstein–Barr virus (EBV) activity of different classes of compounds was assessed by means of an EBV DNA hybridization assay using a digoxigenin-labelled probe specific for the BamHI W fragment of the EBV genome, as well as by measuring viral capsid antigen (VCA) expression after a 7 day incubation period of P3HR-1 producer cells with the test substances. Acyclovir, ganciclovir, cidofovir and zidovudine were included as reference compounds. Several compounds proved to be potent and selective inhibitors of EBV DNA synthesis and VCA expression. Of the new compounds that were evaluated for their anti-EBV activity, the highest efficacy (lowest EC50) and highest selectivity index (SI) were shown by the purine nucleoside analogue 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (S2242) (EC50 0.6 ng/ml; SI 600), the acyclic nucleoside phosphonate analogues 9-(2-phosphonomethoxyethyl)-6-dimethylaminopurine (EC50 1.1 μg/ml; SI 91), 9-(2-phosphonomethoxyethyl)-2-amino-6-benzhydrylaminopurine (EC501.3 μg/ml; SI 29), 7-(2-phosphonomethoxyethyl)-6-dimethylaminopurine (EC50 0.8 μg/ml; SI 56), 9-(R)-(2-phosphonomethoxypropyl)-6-(2-dimethylaminoethyl)-aminopurine (EC50 0.5 μg/ml; SI 42), the 2′,3′-dideoxythymidine derivative 3′-oximino-2′,3′-dideoxythymidine (EC501.5 μg/ml; SI 65), and 1-(2,3-dideoxy-3-N-hydroxyamino-β-d-threo-pentafuran yl)pentafuranosyl)thymine (EC50 4.1 μg/ml; SI >24). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Antiviral Chemistry and Chemotherapy SAGE

Inhibitory Effects of Novel Nucleoside and Nucleotide Analogues on Epstein—Barr Virus Replication:

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Publisher
SAGE
Copyright
Copyright © 2019 by SAGE Publications Ltd unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses
ISSN
2040-2066
eISSN
2040-2066
DOI
10.1177/095632029800900309
Publisher site
See Article on Publisher Site

Abstract

The anti-Epstein–Barr virus (EBV) activity of different classes of compounds was assessed by means of an EBV DNA hybridization assay using a digoxigenin-labelled probe specific for the BamHI W fragment of the EBV genome, as well as by measuring viral capsid antigen (VCA) expression after a 7 day incubation period of P3HR-1 producer cells with the test substances. Acyclovir, ganciclovir, cidofovir and zidovudine were included as reference compounds. Several compounds proved to be potent and selective inhibitors of EBV DNA synthesis and VCA expression. Of the new compounds that were evaluated for their anti-EBV activity, the highest efficacy (lowest EC50) and highest selectivity index (SI) were shown by the purine nucleoside analogue 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (S2242) (EC50 0.6 ng/ml; SI 600), the acyclic nucleoside phosphonate analogues 9-(2-phosphonomethoxyethyl)-6-dimethylaminopurine (EC50 1.1 μg/ml; SI 91), 9-(2-phosphonomethoxyethyl)-2-amino-6-benzhydrylaminopurine (EC501.3 μg/ml; SI 29), 7-(2-phosphonomethoxyethyl)-6-dimethylaminopurine (EC50 0.8 μg/ml; SI 56), 9-(R)-(2-phosphonomethoxypropyl)-6-(2-dimethylaminoethyl)-aminopurine (EC50 0.5 μg/ml; SI 42), the 2′,3′-dideoxythymidine derivative 3′-oximino-2′,3′-dideoxythymidine (EC501.5 μg/ml; SI 65), and 1-(2,3-dideoxy-3-N-hydroxyamino-β-d-threo-pentafuran yl)pentafuranosyl)thymine (EC50 4.1 μg/ml; SI >24).

Journal

Antiviral Chemistry and ChemotherapySAGE

Published: Nov 28, 2016

Keywords: Epstein–Barr virus,nucleoside analogues

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