Antiviral Screening of Multiple Compounds against Ebola Virus

作者：Dowall Stuart D; Bewley Kevin; Watson Robert J; Vasan Seshadri S; Ghosh Chandradhish; Konai Mohini M; Gausdal Gro; Lorens James B; Long Jason; Barclay Wendy; Garcia Dorival Isabel; Hiscox Julian; Bosworth Andrew; Taylor Irene; Easterbrook Linda; Pitman James; Summers Sian; Chan Pensley Jenny; Funnell Simon; Vipond Julia; Charlton Sue; Haldar Jayanta; Hewson Roger; Carroll Miles W

来源：Viruses-Basel, 2016, 8(11): 277.

DOI：10.3390/v8110277

• Ebola virus
• antiviral
• downselection
• drug repurposing

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.

• 出版日期2016-11