Structure and functionality in flavivirus NS-proteins: perspectives for drug design

Autor: Xavier de Lamballerie, Bruno Canard, Ernest A. Gould, Erika J. Mancini, Rene Assenberg, Silvia Speroni, Hélène Malet, Gregory Moureau, Anna M. Jansson, Martino Bolognesi, Barbara Selisko, Johan Neyts, Rolf Hilgenfeld, Michela Bollati, Jonathan M. Grimes, Raymond J. Owens, David I. Stuart, Bruno Coutard, Mario Milani, Holger Steuber, Andrea Mattevi, Eloise Mastrangelo, Jingshan Ren, Cécile Baronti, Etienne Decroly, Torsten Unge, Karin Alvarez, Shelley Cook, Gilda Grard
Jazyk: angličtina
Rok vydání: 2016
Předmět:
ssRNA
single-stranded RNA

Biomedical Research
IMP
Inosine 5′-monophosphate

viruses
NS5RdRp
RNA-dependent RNA polymerase

VIZIER Consortium
Review
Dengue virus
Viral Nonstructural Proteins
VIZIER
Viral Enzymes Involved in Replication

medicine.disease_cause
Virus Replication
NS3Hel
helicase

Communicable Diseases
Emerging

GMP
guanosine monophosphate

GTP
guanosine triphosphate

CCHFV
Crimean-Congo hemorrhagic fever virus

Flavivirus Infections
Enzyme Inhibitors
Methyltransferase
media_common
0303 health sciences
Flaviviral NS3 protein
biology
Flaviviral NS5 protein
2′OMTase
(nucleoside-2′-O-)-methyltransferase

Antivirals
3. Good health
Enzymes
NLS
nuclear localization sequences

Flavivirus
NS
non-structural

HCV
hepatitis C virus

N7MTase
(guanine-N7)-methyltransferase

Polymerase
GTase
guanylyltransferase

medicine.drug_class
CPE
cyto-pathogenic effect

Genomics
HIV
Human Immunodeficiency Virus I

Computational biology
Antiviral Agents
Helicase
ER
endoplasmic reticulum

03 medical and health sciences
Flaviviridae
E
envelope protein

Virology
HBS
high affinity binding site

NS3Pro
protease

medicine
media_common.cataloged_instance
Animals
Humans
European Union
CSFV
classical swine fever virus

European union
030304 developmental biology
Pharmacology
RC
replication-competent complex

NS5MTase
methyltransferase

030306 microbiology
T-705 RMP
T-705-ribofuranosyl-5′-monophosphate

AdoMet
S-adenosyl-L-methionine

LBS
low-affinity binding site

biology.organism_classification
Flavivirus protein structure
Protease
Viral replication
M
membrane protein

Drug Design
C
capsid protein

NS3RTPase
RNA triphosphatase

dsRNA
double-stranded RNA

BVDV
bovine viral diarrhea virus

RSV
respiratory syncytial virus

Antiviral drug
Zdroj: Antiviral Research
Antiviral research
87 (2010): 125–148. doi:10.1016/j.antiviral.2009.11.009
info:cnr-pdr/source/autori:Bollati M.; K. Alvarez; R. Assenberg; C. Baronti; B. Canard; S. Cook; B. Coutard; E. Decroly; X. de Lamballerie; E.A. Gould; G. Grard; J.M. Grimes; R. Hilgenfeld; A.M. Jansson; H. Malet; E.J. Mancini; E. Mastrangelo; A. Mattevi; M. Milani; G. Moureau, J./titolo:Structure and functionality in flavivirus NS-proteins: Perspectives for drug design/doi:10.1016%2Fj.antiviral.2009.11.009/rivista:Antiviral research (Print)/anno:2010/pagina_da:125/pagina_a:148/intervallo_pagine:125–148/volume:87
DOI: 10.1016/j.antiviral.2009.11.009
Popis: 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.
Databáze: OpenAIRE