Easton, Victoria, Mcphillie, Martin, Garcia-Dorival, Isabel 
ORCID: 0000-0002-5654-5662, Barr, John N, Edwards, Thomas A, Foster, Richard, Fishwick, Cohn and Harris, Mark
(2018)
Identification of a small molecule inhibitor of Ebola virus genome replication and transcription using <i>in silico</i> screening.
ANTIVIRAL RESEARCH, 156.
pp. 46-54.
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 (EC<sub>50</sub> 4.8 μM), exhibited low cytotoxicity (CC<sub>50</sub> > 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Ebola virus (EBOV), Nucleoprotein (NP), Small molecule inhibitors (SMIs), Minigenome, Drug discovery |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 26 May 2021 09:59 |
| Last Modified: | 08 Feb 2024 09:52 |
| DOI: | 10.1016/j.antiviral.2018.06.003 |
| Open Access URL: | https://doi.org/10.1016/j.antiviral.2018.06.003 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3124098 |
Dimensions
Dimensions
