Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8523079 | Antiviral Research | 2018 | 37 Pages |
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 4.8â¯Î¼M), exhibited low cytotoxicity (CC50â¯>â¯100â¯Î¼M) 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.
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Authors
Victoria Easton, Martin McPhillie, Isabel Garcia-Dorival, John N. Barr, Thomas A. Edwards, Richard Foster, Colin Fishwick, Mark Harris,