In silico identification, design and synthesis of novel piperazine-based antiviral agents targeting the hepatitis C virus helicase. Eur J Med Chem 2017 Jan 05;125:1115-1131
Date
11/05/2016Pubmed ID
27810598DOI
10.1016/j.ejmech.2016.10.043Scopus ID
2-s2.0-84994045444 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
A structure-based virtual screening of commercial compounds was carried out on the HCV NS3 helicase structure, with the aim to identify novel inhibitors of HCV replication. Among a selection of 13 commercial structures, one compound was found to inhibit the subgenomic HCV replicon in the low micromolar range. Different series of new piperazine-based analogues were designed and synthesised, and among them, several novel structures exhibited antiviral activity in the HCV replicon assay. Some of the new compounds were also found to inhibit HCV NS3 helicase function in vitro, and one directly bound NS3 with a dissociation constant of 570 ± 270 nM.
Author List
Bassetto M, Leyssen P, Neyts J, Yerukhimovich MM, Frick DN, Courtney-Smith M, Brancale AAuthor
David N. Frick PhD Associate Professor in the Chimistry & Biochemistry department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
Antiviral AgentsCell Line
DEAD-box RNA Helicases
Drug Design
Hepacivirus
Hepatitis C
Humans
Molecular Docking Simulation
Nucleoside-Triphosphatase
Piperazines
Replicon
Serine Endopeptidases
Viral Nonstructural Proteins
Virus Replication
