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Flaviviridae are small enveloped viruses hosting a positive-sense single-stranded RNA genome. Besides yellow fever virus, a landmark case in the history of virology, members of the Flavivirus genus, such as West Nile virus and dengue virus, are increasingly gaining attention due to their re-emergence and incidence in different areas of the world. Additional environmental and demographic considerations suggest that novel or known flaviviruses will continue to emerge in the future. Nevertheless, up to few years ago flaviviruses were considered low interest candidates for drug design. At the start of the European Union VIZIER Project, in 2004, just two crystal structures of protein domains from the flaviviral replication machinery were known. Such pioneering studies, however, indicated the flaviviral replication complex as a promising target for the development of antiviral compounds. Here we review structural and functional aspects emerging from the characterization of two main components (NS3 and NS5 proteins) of the flavivirus replication complex. Most of the reviewed results were achieved within the European Union VIZIER Project, and cover topics that span from viral genomics to structural biology and inhibition mechanisms. The ultimate aim of the reported approaches is to shed light on the design and development of antiviral drug leads.

Original publication

DOI

10.1016/j.antiviral.2009.11.009

Type

Journal article

Journal

Antiviral Res

Publication Date

08/2010

Volume

87

Pages

125 - 148

Keywords

Animals, Antiviral Agents, Biomedical Research, Communicable Diseases, Emerging, Drug Design, Enzyme Inhibitors, Enzymes, European Union, Flavivirus, Flavivirus Infections, Humans, Viral Nonstructural Proteins, Virus Replication