Hindered nucleoside analogs as antiflaviviridae agents

Flaviviridae are an important family of viruses, responsible for widely spread diseases such as dengue and West Nile fever and hepatitis C. Despite the severity of the related diseases, no effective antiviral treatments for infection are available. Following our discovery of adenosine-hindered analo...

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Bibliographic Details
Published in:Pure and applied chemistry 2004-01, Vol.76 (5), p.1007-1015
Main Authors: Manfredini, Stefano, Angusti, Angela, Veronese, A. C., Durini, Elisa, Vertuani, S., Nalin, F., Solaroli, N., Pricl, S., Ferrone, Marco, Mura, M., Piano, M. A., Poddesu, B., Cadeddu, Alessandra, Colla, P. La, Loddo, Roberta
Format: Article
Language:English
Subjects:
Analogs
Hepatitis C
Medicin och hälsovetenskap
RNA polymerase
Viral diseases
Viruses
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Summary:Flaviviridae are an important family of viruses, responsible for widely spread diseases such as dengue and West Nile fever and hepatitis C. Despite the severity of the related diseases, no effective antiviral treatments for infection are available. Following our discovery of adenosine-hindered analogs as potent antiflaviviridae agents, we have continued our investigation on guanosine and inosine derivatives, which were evaluated for activity against BVDV, YFV, DENV, and WNV viruses in cell-based assays. The present study allowed us to identify some newer features that led to improve the antiviral potency (down to the µM range) and to selectively inhibit BVDV and YFV viruses. The molecular modeling results were consistent with the hypothesis that test analogs act as RNA-dependent RNA polymerase (RdRp) inhibitors by interacting with a surface allosteric binding pocket.
ISSN:0033-4545
1365-3075
DOI:10.1351/pac200476051007