Abstract
In light of the recent outbreak of Ebola virus (EBOV) disease inWest Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.
Original language | English |
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Article number | 277 |
Journal | Viruses |
Volume | 8 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 2016 |
Bibliographical note
Funding Information:This work was financially supported by the Ebola research funding initiative from the Wellcome Trust to Public Health England (PHE) scientists Miles W. Carroll, Roger Hewson, Julia Vipond, Seshadri Vasan and Simon Funnell (Grant Number 106722/Z/15/Z). The authors would like to thank Keith Spencer from the Wellcome Trust for valuable contributions and discussions in assessing compounds for the suitability for testing. We would also like to thank those organizations that proposed compounds for evaluation, including: University of Liverpool (ouabain and 17-DMAG); BerGenBio (BGB324); Avipero (JB1a); Imperial College London (omeprazole and esomeprazole); Emory University (Gleevec and Tasigna); Daval International (Aimspro); Jawaharlal Nehru Centre for Advanced Scientific Research (NCK-8 and D-LANA-14); and 60? Pharmaceuticals (celgosivir and castanospermine). The views expressed in this report are those of the authors and not necessarily those of the employing institutions or the funding body.
Publisher Copyright:
© 2016 by the authors; licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
Keywords
- Antiviral
- Downselection
- Drug repurposing
- Ebola virus