NTPase/helicase of Flaviviridae: inhibitors and inhibition of the enzyme.
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.
Borowski
Peter
P
Abteilung für Virologie, Bernhard-Nocht-Institut für Tropenmedizin, Hamburg, Germany. borowski@bni.uni.hamburg.de
Niebuhr
Andreas
A
Schmitz
Herbert
H
Hosmane
Ramachandra S
RS
Bretner
Maria
M
Siwecka
Maria A
MA
Kulikowski
Tadeusz
T
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
D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins; D017766:Acid Anhydride Hydrolases; D043583:Nucleoside-Triphosphatase; D004265:DNA Helicases