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 |
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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 |
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