In silico identification, design and synthesis of novel piperazine-based antiviral agents targeting the hepatitis C virus helicase

Bassetto, Marcella, Leyssen, Pieter, Neyts, Johan, Yerukhimovich, Mark M., Frick, David N., Courtney-Smith, Matthew and Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419 2017. In silico identification, design and synthesis of novel piperazine-based antiviral agents targeting the hepatitis C virus helicase. European Journal of Medicinal Chemistry 125 , pp. 1115-1131. 10.1016/j.ejmech.2016.10.043

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords:	Structure-based virtual screening; HCV NS3-helicase; Piperazine derivatives; Anti-HCV activity; NS3 helicase inhibitors
Publisher:	Elsevier
ISSN:	0223-5234
Date of First Compliant Deposit:	18 November 2016
Date of Acceptance:	18 October 2016
Last Modified:	08 Jan 2024 18:53
URI:	https://orca.cardiff.ac.uk/id/eprint/96259

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