Discovery of a novel HCV helicase inhibitor by a de novo drug design approach.
Herein we report a successful application of a computer-aided design approach to identify a novel HCV helicase inhibitor. A de novo drug design methodology was used to generate an initial set of structures that could potentially bind to a putative binding site. Further structure refinement was carried out through docking a series of focused virtual libraries. The most promising compound was synthesised and it exhibited a submicromolar inhibition of the HCV helicase.
The Welsh School of Pharmacy, Cardiff University, Cardiff, United Kingdom.
Sahar
S
Kandil
Sonia
S
Biondaro
Dimitrios
D
Vlachakis
Anna-Claire
AC
Cummins
Antonio
A
Coluccia
Colin
C
Berry
Pieter
P
Leyssen
Johan
J
Neyts
Andrea
A
Brancale
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016174:Hepacivirus / Q000201:enzymology*; D020365:RNA Helicases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D020365:RNA Helicases; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases