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.
Highlights
Ebolavirus is a genus of the family Filoviridae and includes five species: Bundibugyo virus (BDBV), Reston virus (RESTV), Sudan virus (SUDV), Taï Forest virus (TAFV) and Ebola virus (EBOV).Ebola virus is the prototype species [1,2] and was responsible for the large outbreak of Ebola virus disease (EVD) in parts of West Africa first recognized in December [3]
Due to the large number of compounds initially proposed for antiviral testing, a scoring assessment was undertaken to triage compounds in relation to the capacity available for testing at Containment Level 4 (CL4)
BGB324was wasdelivered delivered orally with doses per starting day starting at 6 h post‐challenge
Summary
Ebolavirus is a genus of the family Filoviridae and includes five species: Bundibugyo virus (BDBV), Reston virus (RESTV), Sudan virus (SUDV), Taï Forest virus (TAFV) and Ebola virus (EBOV).Ebola virus is the prototype species [1,2] (formally designated Zaire ebolavirus) and was responsible for the large outbreak of Ebola virus disease (EVD) in parts of West Africa first recognized in December [3]. Ebolavirus is a genus of the family Filoviridae and includes five species: Bundibugyo virus (BDBV), Reston virus (RESTV), Sudan virus (SUDV), Taï Forest virus (TAFV) and Ebola virus (EBOV). In response to the outbreak in West Africa and the threat of further outbreaks in the absence of approved and proven therapeutics or vaccines, there has been increased international, political, humanitarian and scientific momentum to identify treatment strategies. In this context, during the 2013/2014 EBOV outbreak, Public Health England (PHE) was approached by several academic and commercial entities requesting rapid evaluation of repurposed drugs and experimental therapies for EBOV, using its Containment Level 4 (CL4) facilities. Brief details of the compounds nominated for inclusion are outlined below:
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
