Finding New Medicines for Flaviviral Targets

  1. Gregory Bock Organizer and
  2. Jamie Goode
  1. Thomas H. Keller,
  2. Yen Liang Chen,
  3. John E. Knox,
  4. Siew Pheng Lim,
  5. Ngai Ling Ma,
  6. Sejal J. Patel,
  7. Aruna Sampath,
  8. Qing Yin Wang,
  9. Zheng Yin and
  10. Subhash G. Vasudevan

Published Online: 7 OCT 2008

DOI: 10.1002/0470058005.ch8

New Treatment Strategies for Dengue and Other Flaviviral Diseases: Novartis Foundation Symposium 277

New Treatment Strategies for Dengue and Other Flaviviral Diseases: Novartis Foundation Symposium 277

How to Cite

Keller, T. H., Chen, Y. L., Knox, J. E., Lim, S. P., Ling Ma, N., Patel, S. J., Sampath, A., Wang, Q. Y., Yin, Z. and Vasudevan, S. G. (2008) Finding New Medicines for Flaviviral Targets, in New Treatment Strategies for Dengue and Other Flaviviral Diseases: Novartis Foundation Symposium 277 (eds G. Bock and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/0470058005.ch8

Author Information

  1. Novartis Institute for Tropical Diseases (NITD), 10 Biopolis Road, Chromos #05-01, Singapore 138670

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 25 AUG 2006

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470016435

Online ISBN: 9780470058008

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Keywords:

  • anti-flaviviral therapeutics and NS5 polymerase;
  • Scintillation Proximity Assay (SPA);
  • NS3 helicase drug target in flaviviral diseases;
  • dengue drug - target product profile (TPP);
  • FRET (fluorescence resonance energy transfer)-based helicase unwinding assay

Summary

With the incidence of dengue fever increasing all over the world, there is an urgent need for therapies. While drug discovery for any disease is a long and difficult process with uncertain success, dengue fever poses an additional complication in that most of the target patient population is young and lives in developing countries with very limited health care budgets. Recent progress in drug discovery for dengue and an analysis of approaches toward hepatitis C virus (HCV) therapeutics suggest that NS5 polymerase is the most promising target for dengue. Moreover such inhibitors may be useful for several other flaviviral diseases. NS3 proteases will be more challenging targets, especially if oral delivery is desired. Recent work has shown that potent inhibitors can be designed readily, but optimization of pharmacokinetic parameters will probably be a long an arduous task, especially since the primary binding pockets prefer to bind basic amino acids. NS3 helicase can also be considered a viable drug target for flaviviral diseases. It has however proved to be a challenging for HCV and selectivity issues versus human helicases must be overcome.