title: Structure and functionality in flavivirus NS-proteins: perspectives for drug design.
abstract: 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.
authors: Department of Biomolecular Sciences and Biotechnology, University of Milano, Via Celoria 26, 20133 Milano, Italy.
authors: Michela
authors: M
authors: Bollati
authors: Karin
authors: K
authors: Alvarez
authors: René
authors: R
authors: Assenberg
authors: Cécile
authors: C
authors: Baronti
authors: Bruno
authors: B
authors: Canard
authors: Shelley
authors: S
authors: Cook
authors: Bruno
authors: B
authors: Coutard
authors: Etienne
authors: E
authors: Decroly
authors: Xavier
authors: X
authors: de Lamballerie
authors: Ernest A
authors: EA
authors: Gould
authors: Gilda
authors: G
authors: Grard
authors: Jonathan M
authors: JM
authors: Grimes
authors: Rolf
authors: R
authors: Hilgenfeld
authors: Anna M
authors: AM
authors: Jansson
authors: Hélène
authors: H
authors: Malet
authors: Erika J
authors: EJ
authors: Mancini
authors: Eloise
authors: E
authors: Mastrangelo
authors: Andrea
authors: A
authors: Mattevi
authors: Mario
authors: M
authors: Milani
authors: Grégory
authors: G
authors: Moureau
authors: Johan
authors: J
authors: Neyts
authors: Raymond J
authors: RJ
authors: Owens
authors: Jingshan
authors: J
authors: Ren
authors: Barbara
authors: B
authors: Selisko
authors: Silvia
authors: S
authors: Speroni
authors: Holger
authors: H
authors: Steuber
authors: David I
authors: DI
authors: Stuart
authors: Torsten
authors: T
authors: Unge
authors: Martino
authors: M
authors: Bolognesi
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D035843:Biomedical Research / Q000458:organization & administration / Q000639:trends; D021821:Communicable Diseases, Emerging / Q000453:epidemiology / Q000821:virology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004798:Enzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005062:European Union; D005416:Flavivirus / Q000187:drug effects / Q000201:enzymology*; D018177:Flavivirus Infections / Q000453:epidemiology / Q000821:virology; D006801:Humans; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D004798:Enzymes; D017361:Viral Nonstructural Proteins