title: Antiviral Screening of Multiple Compounds against Ebola Virus.
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.
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. stuart.dowall@phe.gov.uk.|Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, UK. stuart.dowall@phe.gov.uk.
authors: Stuart D
authors: SD
authors: Dowall
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. kevin.bewley@phe.gov.uk.
authors: Kevin
authors: K
authors: Bewley
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. robert.watson@phe.gov.uk.
authors: Robert J
authors: RJ
authors: Watson
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. seshadri.vasan@phe.gov.uk.|Department of Preventive and Social Medicine, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry 605006, India. seshadri.vasan@phe.gov.uk.
authors: Seshadri S
authors: SS
authors: Vasan
authors: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 560064, Karnataka, India. chandradhish@jncasr.ac.in.
authors: Chandradhish
authors: C
authors: Ghosh
authors: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 560064, Karnataka, India. mohinimk@jncasr.ac.in.
authors: Mohini M
authors: MM
authors: Konai
authors: BerGenBio, Jonas Lies vei 91, Bergen 5009, Norway. gro.gausdal@bergenbio.com.
authors: Gro
authors: G
authors: Gausdal
authors: BerGenBio, Jonas Lies vei 91, Bergen 5009, Norway. jim.lorens@bergenbio.com.
authors: James B
authors: JB
authors: Lorens
authors: Imperial College London, St Mary's Campus, London W2 1PG, UK. jason.long08@imperial.ac.uk.
authors: Jason
authors: J
authors: Long
authors: Imperial College London, St Mary's Campus, London W2 1PG, UK. w.barclay@imperial.ac.uk.
authors: Wendy
authors: W
authors: Barclay
authors: Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, UK. g.garcia-dorival@liverpool.ac.uk.
authors: Isabel
authors: I
authors: Garcia-Dorival
authors: Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, UK. julian.hiscox@liverpool.ac.uk.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, UK. julian.hiscox@liverpool.ac.uk.
authors: Julian
authors: J
authors: Hiscox
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. andrew.bosworth@phe.gov.uk.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, UK. andrew.bosworth@phe.gov.uk.
authors: Andrew
authors: A
authors: Bosworth
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. irene.taylor@phe.gov.uk.
authors: Irene
authors: I
authors: Taylor
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. linda.easterbrook@phe.gov.uk.
authors: Linda
authors: L
authors: Easterbrook
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. james.pitman@phe.gov.uk.
authors: James
authors: J
authors: Pitman
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. sian.summers@phe.gov.uk.
authors: Sian
authors: S
authors: Summers
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. jenny.chan-pensley@phe.gov.uk.
authors: Jenny
authors: J
authors: Chan-Pensley
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. simon.funnell@phe.gov.uk.
authors: Simon
authors: S
authors: Funnell
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. julia.vipond@phe.gov.uk.
authors: Julia
authors: J
authors: Vipond
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. sue.charlton@phe.gov.uk.
authors: Sue
authors: S
authors: Charlton
authors: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 560064, Karnataka, India. jayanta@jncasr.ac.in.
authors: Jayanta
authors: J
authors: Haldar
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. roger.hewson@phe.gov.uk.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, UK. roger.hewson@phe.gov.uk.
authors: Roger
authors: R
authors: Hewson
authors: Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. miles.carroll@phe.gov.uk.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, UK. miles.carroll@phe.gov.uk.
authors: Miles W
authors: MW
authors: Carroll
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D029043:Ebolavirus / Q000187:drug effects*; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy; D006801:Humans; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents
keywords: Ebola virus; antiviral; downselection; drug repurposing