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Publicly Available Published by De Gruyter January 1, 2009

Hindered nucleoside analogs as antiflaviviridae agents

  • Stefano Manfredini , Angela Angusti , A. C. Veronese , Elisa Durini , S. Vertuani , F. Nalin , N. Solaroli , S. Pricl , Marco Ferrone , M. Mura , M. A. Piano , B. Poddesu , Alessandra Cadeddu , P. La Colla and Roberta Loddo

Abstract

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.


Conference

Polish-Austrian-German-Hungarian-Italian Joint Meeting on Medicinal Chemistry, Kraków, Poland, 2003-10-15–2003-10-18


Published Online: 2009-01-01
Published in Print: 2004-01-01

© 2013 Walter de Gruyter GmbH, Berlin/Boston

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