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. 2016 Oct 27;8(11):277.
doi: 10.3390/v8110277.

Antiviral Screening of Multiple Compounds against Ebola Virus

Stuart D Dowall  1   2 , Kevin Bewley  3 , Robert J Watson  4 , Seshadri S Vasan  5   6 , Chandradhish Ghosh  7 , Mohini M Konai  8 , Gro Gausdal  9 , James B Lorens  10 , Jason Long  11 , Wendy Barclay  12 , Isabel Garcia-Dorival  13 , Julian Hiscox  14   15 , Andrew Bosworth  16   17 , Irene Taylor  18 , Linda Easterbrook  19 , James Pitman  20 , Sian Summers  21 , Jenny Chan-Pensley  22 , Simon Funnell  23 , Julia Vipond  24 , Sue Charlton  25 , Jayanta Haldar  26 , Roger Hewson  27   28 , Miles W Carroll  29   30
Affiliations

Antiviral Screening of Multiple Compounds against Ebola Virus

Stuart D Dowall et al. Viruses. .

Abstract

In light of the recent outbreak of Ebola virus (EBOV) disease in West 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.

Keywords: Ebola virus; antiviral; downselection; drug repurposing.

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Conflict of interest statement

PHE authors claim no conflicts of interest. The remaining authors contributed reagents, which formed part of their institution/company work programs; however, these authors had no role in the collection, analyses or interpretation of data, nor in the writing of the manuscript.

Figures

Figure 1
Figure 1
Survival and clinical parameters of guinea pigs treated with 100 mg/kg BGB324 twice daily compared to untreated controls (n = 6 per group). (a) Survival analysis after challenge with 103 TCID50 EBOV; (b) Weight changes as a percentage compared to the day of challenge; (c) Temperature changes as °C difference compared to the day of challenge.
Figure 2
Figure 2
Survival and clinical parameters of guinea pigs treated with 5 mg/kg NCK-8 twice daily compared to untreated controls (n = 6 per group). (a) Survival analysis after challenge with 103 TCID50 EBOV; (b) Weight changes as a percentage compared to the day of challenge; (c) Temperature changes as °C difference compared to the day of challenge.
See this image and copyright information in PMC

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