Easton, V, McPhillie, M, Garcia-Dorival, I et al. (5 more authors) (2018) Identification of a small molecule inhibitor of Ebolavirus genome replication and transcription using in silico screening. Antiviral Research, 156. pp. 46-54. ISSN 0166-3542
Abstract
Ebola virus (EBOV) causes a severe haemorrhagic fever in humans and has a mortality rate over 50%. With no licensed drug treatments available, EBOV poses a significant threat. Investigations into possible therapeutics have been severely hampered by the classification of EBOV as a BSL4 pathogen. Here, we describe a drug discovery pathway combining in silico screening of compounds predicted to bind to a hydrophobic pocket on the nucleoprotein (NP); with a robust and rapid EBOV minigenome assay for inhibitor validation at BSL2. One compound (MCCB4) was efficacious (EC50 4.8 μM), exhibited low cytotoxicity (CC50 > 100 μM) and was specific, with no effect on either a T7 RNA polymerase driven firefly luciferase or a Bunyamwera virus minigenome. Further investigations revealed that this small molecule inhibitor was able to outcompete established replication complexes, an essential aspect for a potential EBOV treatment.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 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: | Ebola virus (EBOV); Nucleoprotein (NP); Small molecule inhibitors (SMIs); Minigenome; Drug discovery |
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) > Virology 1 (Leeds) The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 14 Jun 2018 13:53 |
Last Modified: | 25 Jun 2023 21:23 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.antiviral.2018.06.003 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:132032 |