Understanding helicases as a means of virus control.
Helicases are promising antiviral drug targets because their enzymatic activities are essential for viral genome replication, transcription, and translation. Numerous potent inhibitors of helicases encoded by herpes simplex virus, severe acute respiratory syndrome coronavirus, hepatitis C virus, Japanese encephalitis virus, West Nile virus, and human papillomavirus have been recently reported in the scientific literature. Some inhibitors have also been shown to decrease viral replication in cell culture and animal models. This review discusses recent progress in understanding the structure and function of viral helicases to help clarify how these potential antiviral compounds function and to facilitate the design of better inhibitors. The above helicases and all related viral proteins are classified here based on their evolutionary and functional similarities, and the key mechanistic features of each group are noted. All helicases share a common motor function fueled by ATP hydrolysis, but differ in exactly how the motor moves the protein and its cargo on a nucleic acid chain. The helicase inhibitors discussed here influence rates of helicase-catalyzed DNA (or RNA) unwinding by preventing ATP hydrolysis, nucleic acid binding, nucleic acid release, or by disrupting the interaction of a helicase with a required cofactor.
Frick
D N
DN
Department of Biochemistry & Molecular Biology, New York Medical College, Valhalla, NY 10595, USA. David_Frick@NYMC.edu
Lam
A M I
AM
D000998:Antiviral Agents / Q000494:pharmacology*; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D019915:DNA Primase / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D027383:Papillomaviridae / Q000187:drug effects / Q000201:enzymology; D020365:RNA Helicases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects / Q000201:enzymology; D012697:Serine Endopeptidases; D018139:Simplexvirus / Q000187:drug effects / Q000201:enzymology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D004265:DNA Helicases; D019915:DNA Primase; D004791:Enzyme Inhibitors; D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C084422:NS3 protein, hepatitis C virus; C062021:helicase-primase, Human herpesvirus 1