Shaw, J, Fishwick, C and Harris, M (2015) Epoxide based inhibitors of the hepatitis C virus non-structural 2 autoprotease. Antiviral Research, 117. 20 - 26. ISSN 0166-3542
Abstract
Hepatitis C virus (HCV) non-structural 2 (NS2) encodes an essential protease activity responsible for processing at the NS2-NS3 junction which represents an attractive antiviral target. Attempts to inhibit the NS2 autoprotease with mechanism-based protease inhibitors and substrate peptides have had limited success. We report a series of epoxide-containing small molecules capable of blocking NS2-NS3 proteolysis in vitro and demonstrate the potential for selectivity towards the NS2 autoprotease. A compound within this series was able to perturb HCV genome replication in a subgenomic replicon system only when polyprotein processing was dependent on NS2 autoprotease activity, in addition it inhibited replication of full length HCV. These findings suggest blocking HCV polyprotein processing through inhibition of the NS2 autoprotease represents a viable route to exert an antiviral effect.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). |
Keywords: | Hepatitis C virus; autoprotease; epoxide; inhibitor; NS2 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 20 Apr 2015 12:19 |
Last Modified: | 17 Aug 2015 13:36 |
Published Version: | http://dx.doi.org/10.1016/j.antiviral.2015.02.005 |
Status: | Published |
Publisher: | Elsevier Masson |
Refereed: | Yes |
Identification Number: | 10.1016/j.antiviral.2015.02.005 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:84051 |