title: NTPase/helicase of Flaviviridae: inhibitors and inhibition of the enzyme.
abstract: RNA nucleoside triphosphatases (NTPase)/helicases represent a large family of proteins that are ubiquitously distributed over a wide range of organisms. The enzymes play essential role in cell development and differentiation, and some of them are involved in transcription and replication of viral single-stranded RNA genomes. The enzymatic activities of a NTPase/helicase were also detected in the carboxyl-terminal non-structural protein 3 (NS3) of members of the Flaviviridae family. The crucial role of the enzyme for the virus life cycle was demonstrated in knock out experiments and by using NTPase/helicase specific inhibitors. This makes the enzyme an attractive target for development of Flaviviridae-specific antiviral therapies. This review will summarize our knowledge about the function and structure of the enzyme, update the spectrum of inhibitors of the enzymatic activities of the NTPase/helicase and describe the different mechanisms by which the compounds act. Some of the compounds reviewed herein could show potential utility as antiviral agents against Flaviviridae viruses.
authors.affiliation: Abteilung für Virologie, Bernhard-Nocht-Institut für Tropenmedizin, Hamburg, Germany. borowski@bni.uni.hamburg.de
authors.forename: Peter
authors.initials: P
authors.lastname: Borowski
authors.forename: Andreas
authors.initials: A
authors.lastname: Niebuhr
authors.forename: Herbert
authors.initials: H
authors.lastname: Schmitz
authors.forename: Ramachandra S
authors.initials: RS
authors.lastname: Hosmane
authors.forename: Maria
authors.initials: M
authors.lastname: Bretner
authors.forename: Maria A
authors.initials: MA
authors.lastname: Siwecka
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Kulikowski
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D018067:Flaviviridae / Q000201:enzymology* / Q000235:genetics; D016679:Genome, Viral; D006801:Humans; D008958:Models, Molecular; D043583:Nucleoside-Triphosphatase; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins; D017766:Acid Anhydride Hydrolases; D043583:Nucleoside-Triphosphatase; D004265:DNA Helicases