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Wednesday, 17 February 2016

The Medicinal Chemistry of Dengue Virus

Abstract Image

The dengue virus and related flaviviruses are an increasing global health threat. In this perspective, we comment on and review medicinal chemistry efforts aimed at the prevention or treatment of dengue infections. We include target-based approaches aimed at viral or host factors and results from phenotypic screenings in cellular assay systems for viral replication. This perspective is limited to the discussion of results that provide explicit chemistry or structure–activity relationship (SAR), or appear to be of particular interest to the medicinal chemist for other reasons. The discovery and development efforts discussed here may at least partially be extrapolated toward other emerging flaviviral infections, such as West Nile virus. Therefore, this perspective, although not aimed at flaviviruses in general, should also be able to provide an overview of the medicinal chemistry of these closely related infectious agents.


The Medicinal Chemistry of Dengue Virus

Medicinal Chemistry, Institute of Pharmacy and Molecular Biotechnology IPMB, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany
§ Laboratory of Organic Synthesis, Institute of Chemistry of the Academy of Sciences of Moldova, Academiei 3, 2028 Chisinau, Moldova
J. Med. Chem., Article ASAP
DOI: 10.1021/acs.jmedchem.5b01653
Publication Date (Web): January 15, 2016
Copyright © 2016 American Chemical Society
*C. D. Klein, phone +49-6221-544875, e-mail c.klein@uni-heidelberg.de.
ACS Editors' Choice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

Mira A. M. Behnam studied pharmacy and biotechnology at The German University in Cairo, where she obtained her B.Sc. degree (2009) and M.Sc. degree (2011) in Pharmaceutical Chemistry in collaboration with Würzburg University. Since 2013, she is DAAD scholarship holder and Ph.D. candidate in the group of Prof. Christian Klein (Heidelberg University) working on the development of potent antiviral compounds against dengue and West Nile virus.
Christoph Nitsche studied chemistry and business administration. He obtained his Ph.D. on the development of dengue virus protease inhibitors under the guidance of Prof. Christian Klein at Heidelberg University with a scholarship from the German National Academic Foundation. Currently, he is working as a Feodor Lynen Fellow (Alexander von Humboldt-Foundation) in the laboratory of Prof. Gottfried Otting at the Australian National University. His present research focuses on novel NMR methods for drug discovery.
Veaceslav Boldescu studied pharmaceutical technology and obtained a Ph.D. in Technology of special products (pharmaceuticals) in 2008 under the guidance of Acad. Gheorghe Duca (Academy of Sciences of Moldova). He started his research pathway at the State University of Moldova and continued it at the Institute of Chemistry of the Academy of Sciences of Moldova, working in the Laboratory of Organic Synthesis lead by Prof. Fliur Macaev. His main research interests include development of new chemotherapeutic agents against infections such as tuberculosis and dengue.
Christian D. Klein studied pharmacy and obtained a Ph.D. in Pharmaceutical Chemistry in 2000 under the guidance of Profs. Ulrike Holzgrabe (University of Bonn) and A. J. Hopfinger (UIC, Chicago). Following postdoctoral work at ETH Zürich, he became an Emmy Noether junior group leader. Since 2007, he is professor of Pharmaceutical Chemistry at Heidelberg University. His main research interests are anti-infective compounds and fundamental questions in medicinal chemistry, such as the study of unusual binding modes and structural motifs.