TY - JOUR
T1 - Structure and functionality in flavivirus NS-Proteins: Perspectives for drug design
AU - Bollati, Michela
AU - Alvarez, Karin
AU - Assenberg, René
AU - Baronti, Cécile
AU - Canard, Bruno
AU - Cook, Shelley
AU - Coutard, Bruno
AU - Decroly, Etienne
AU - de Lamballerie, Xavier
AU - Gould, Ernest A.
AU - Grard, Gilda
AU - Grimes, Jonathan M.
AU - Hilgenfeld, Rolf
AU - Jansson, Anna M.
AU - Malet, Hélène
AU - Mancini, Erika J.
AU - Mastrangelo, Eloise
AU - Mattevi, Andrea
AU - Milani, Mario
AU - Moureau, Grégory
AU - Neyts, Johan
AU - Owens, Raymond J.
AU - Ren, Jingshan
AU - Selisko, Barbara
AU - Speroni, Silvia
AU - Steuber, Holger
AU - Stuart, David I.
AU - Unge, Torsten
AU - Bolognesi, Martino
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77954956665&partnerID=8YFLogxK
U2 - 10.1016/j.antiviral.2009.11.009
DO - 10.1016/j.antiviral.2009.11.009
M3 - Scientific review articles
C2 - 19945487
AN - SCOPUS:77954956665
SN - 0166-3542
VL - 87
SP - 125
EP - 148
JO - Antiviral Research
JF - Antiviral Research
IS - 2
ER -