{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T09:29:04Z","timestamp":1780824544974,"version":"3.54.1"},"reference-count":33,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T00:00:00Z","timestamp":1587081600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000014","name":"Canadian Blood Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000014","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000008","name":"Health Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000008","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    There continues to be no approved drugs for the treatment of Ebola virus disease (EVD). Despite a number of candidate drugs showing limited efficacy\n                    <ns4:italic>in vitro<\/ns4:italic>\n                    and\/or in non-human primate studies, EVD continues to plaque certain areas of Africa without any efficacious treatments yet available. Recently, we have been exploring the potential for anti-malarial drugs to inhibit an\n                    <ns4:italic>in vitro<\/ns4:italic>\n                    model of Ebola Zaire replication using a transcription-competent virus-like particle (trVLP) assay. We examined the efficacy of chloroquine, amodiaquine and 36 novel anti-parasite quinoline derivatives at inhibiting Ebola virus replication. Drug efficacy was tested by trVLP assay and toxicity by MTT assay. Both chloroquine and amodiaquine were effective for inhibition of Ebola virus replication without significant toxicity. The half-maximal inhibitory concentration (IC\n                    <ns4:sub>50<\/ns4:sub>\n                    ) of chloroquine and amodiaquine to inhibit Ebola virus replication were IC\n                    <ns4:sub>50, Chl<\/ns4:sub>\n                    = 3.95 \u00b5M and IC\n                    <ns4:sub>50, Amo<\/ns4:sub>\n                    = 1.45 \u00b5M, respectively. Additionally, three novel quinoline derivatives were identified as having inhibitory activity and low toxicity for Ebola trVLP replication, with 2NH2Q being the most promising derivative, with an IC\n                    <ns4:sub>50<\/ns4:sub>\n                    of 4.66 \u00b5M. Quinoline compounds offer many advantages for disease treatment in tropical climates as they are cheap to produce, easy to synthesize and chemically stable. In this report, we have demonstrated the potential of anti-parasite quinolines for further investigation for use in EVD.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.22352.1","type":"journal-article","created":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T14:15:21Z","timestamp":1587132921000},"page":"268","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Inhibition of in vitro Ebola infection by anti-parasitic quinoline derivatives"],"prefix":"10.12688","volume":"9","author":[{"given":"Shawn","family":"Goyal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Binnington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.S.","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Desma\u00eble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"F\u00e9rri\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4226-8489","authenticated-orcid":false,"given":"Bruno","family":"Figad\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8542-6793","authenticated-orcid":false,"given":"Philippe M.","family":"Loiseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald R.","family":"Branch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2020,4,17]]},"reference":[{"key":"ref-1","article-title":"WHO | Ebola virus disease.","year":"2018"},{"key":"ref-2","article-title":"Ebola | Ebola situation reports: Democratic Republic of the Congo.","year":"2019"},{"key":"ref-3","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2016.0297","article-title":"The Ebola outbreak, 2013-2016: old lessons for new epidemics.","volume":"372","author":"C Coltart","year":"2017","journal-title":"Philos Trans R Soc Lond B Biol Sci."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"88-94","DOI":"10.1016\/j.coviro.2017.03.008","article-title":"Immunomonitoring of human responses to the rVSV-ZEBOV Ebola vaccine.","volume":"23","author":"D Medaglini","year":"2017","journal-title":"Curr Opin Virol."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"444-51","DOI":"10.1016\/j.aogh.2015.02.005","article-title":"Transmission of ebola virus disease: an overview.","volume":"80","author":"S Rewar","year":"2014","journal-title":"Ann Glob Heal."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"1468-73","DOI":"10.3201\/eid0812.010317","article-title":"Identifying reservoirs of infection: a conceptual and practical challenge.","volume":"8","author":"D Haydon","year":"2002","journal-title":"Emerg Infect Dis."},{"key":"ref-7","article-title":"DR Congo Ebola outbreak: Beni attack halts outreach work."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"34","DOI":"10.12688\/f1000research.6110.1","article-title":"Virtual screen for repurposing approved and experimental drugs for candidate inhibitors of EBOLA virus infection [version 2; peer review: 2 approved].","volume":"4","author":"V Veljkovic","year":"2015","journal-title":"F1000Res."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"e60579","DOI":"10.1371\/journal.pone.0060579","article-title":"A systematic screen of FDA-approved drugs for inhibitors of biological threat agents.","volume":"8","author":"P Madrid","year":"2013","journal-title":"PLoS One."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"23-32","DOI":"10.1056\/NEJMoa1504605","article-title":"Effect of Artesunate\u2013Amodiaquine on Mortality Related to Ebola Virus Disease.","volume":"374","author":"E Gignoux","year":"2016","journal-title":"N Engl J Med."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"3847-3850","DOI":"10.1016\/S0040-4039(01)00604-9","article-title":"Expeditious preparation of 2-substituted quinolines.","volume":"42","author":"M Fakhfakh","year":"2001","journal-title":"TETRAHEDRON LETT."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"5013-23","DOI":"10.1016\/j.bmc.2003.09.007","article-title":"Synthesis and biological evaluation of substituted quinolines: Potential treatment of protozoal and retroviral co-infections.","volume":"11","author":"M Fakhfakh","year":"2003","journal-title":"Bioorganic Med Chem."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"11-20","DOI":"10.1007\/s40883-018-0045-3","article-title":"New Water-Soluble Polymeric Prodrugs of 2-n-propylquinoline: Synthesis and Evaluation of In Vitro and In Vivo Activities Against Leishmania donovani.","volume":"4","author":"V Ravichandran","year":"2018","journal-title":"Regen Eng Transl Med."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"2863-75","DOI":"10.1081\/SCC-120006472","article-title":"Preparation of quinolines substituted at the 2 or 3 position by an alkenyl or alkynyl chain.","volume":"32","author":"M Fakhfakh","year":"2002","journal-title":"Synth Commun."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"4494-7","DOI":"10.1039\/b815963g","article-title":"Oxidation of antiparasitic 2-substituted quinolines using metalloporphyrin catalysts: Scale-up of a biomimetic reaction for metabolite production of drug candidates.","volume":"6","author":"B Akagah","year":"2008","journal-title":"Org Biomol Chem."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"186-8","DOI":"10.1016\/j.biopha.2007.02.001","article-title":"In vitro and in vivo antileishmanial efficacy of a new nitrilquinoline against Leishmania donovani.","volume":"61","author":"H Nakayama","year":"2007","journal-title":"Biomed Pharmacother."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"430-5","DOI":"10.1016\/j.biopha.2007.05.003","article-title":"Quinoline compounds decrease in vitro spontaneous proliferation of peripheral blood mononuclear cells (PBMC) from human T-cell lymphotropic virus (HTLV) type-1-infected patients.","volume":"62","author":"F Grassi","year":"2008","journal-title":"Biomed Pharmacother."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"e6215","DOI":"10.1371\/journal.pone.0006215","article-title":"Chemicals possessing a neurotrophin-like activity on dopaminergic neurons in primary culture.","volume":"4","author":"F Schmidt","year":"2009","journal-title":"PLoS One."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"891-4","DOI":"10.1016\/s0960-894x(02)01085-5","article-title":"Substituted quinolines induce inhibition of proliferation of HTLV-1 infected cells.","volume":"13","author":"A Fournet","year":"2003","journal-title":"Bioorganic Med Chem Lett."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"4019-22","DOI":"10.1016\/j.bmcl.2005.06.036","article-title":"New HIV-1 replication inhibitors of the styryquinoline class bearing aroyl\/acyl groups at the C-7 position: Synthesis and biological activity.","volume":"15","author":"M Normand-Bayle","year":"2005","journal-title":"Bioorganic Med Chem Lett."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"1777-80","DOI":"10.1128\/AAC.01299-10","article-title":"In vitro activities of new 2-substituted quinolines against Leishmania donovani.","volume":"55","author":"P Loiseau","year":"2011","journal-title":"Antimicrob Agents Chemother."},{"key":"ref-22","article-title":"\u201cInhibition of in vitro Ebola infection by anti-parasite quinoline derivatives\u201d.","author":"S Goyal","year":"2020"},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"2846-57","DOI":"10.1021\/jm980043e","article-title":"Styrylquinoline derivatives: A new class of potent HIV-1 integrase inhibitors that block HIV-1 replication in CEM cells.","volume":"41","author":"K Mekouar","year":"1998","journal-title":"J Med Chem."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"1533-40","DOI":"10.1021\/jm990467o","article-title":"Structure-activity relationships and binding mode of styrylquinolines as potent inhibitors of HIV-1 integrase and replication of HIV-1 in cell culture.","volume":"43","author":"F Zouhiri","year":"2000","journal-title":"J Med Chem."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"2473-6","DOI":"10.1016\/j.bmcl.2004.03.005","article-title":"Linker-modified quinoline derivatives targeting HIV-1 integrase: Synthesis and biological activity.","volume":"14","author":"C B\u00e9nard","year":"2004","journal-title":"Bioorganic Med Chem Lett."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"4950-6","DOI":"10.1128\/AAC.49.12.4950-4956.2005","article-title":"Efficacy of orally administered 2-substituted quinolines in experimental murine cutaneous and visceral leishmaniases.","volume":"49","author":"H Nakayama","year":"2005","journal-title":"Antimicrob Agents Chemother."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"52381","DOI":"10.3791\/52381","article-title":"Modeling the lifecycle of ebola virus under biosafety level 2 conditions with virus-like particles containing tetracistronic minigenomes.","author":"T Hoenen","year":"2014","journal-title":"J Vis Exp."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"119-31","DOI":"10.1007\/978-1-4939-7116-9_9","article-title":"Modeling the Ebolavirus Life Cycle with Transcription and Replication-Competent Viruslike Particle Assays.","volume":"1628","author":"N Biedenkopf","year":"2017","journal-title":"Methods Mol Biol."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"e0004364","DOI":"10.1371\/journal.pntd.0004364","article-title":"A Rapid Screening Assay Identifies Monotherapy with Interferon-\u00df and Combination Therapies with Nucleoside Analogs as Effective Inhibitors of Ebola Virus","volume":"10","author":"S McCarthy","year":"2016","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"226-37","DOI":"10.1016\/j.antiviral.2018.08.013","article-title":"High-throughput drug screening using the Ebola virus transcription- and replication-competent virus-like particle system.","volume":"158","author":"N Lee","year":"2018","journal-title":"Antiviral Res."},{"key":"ref-31","doi-asserted-by":"publisher","first-page":"73-83","DOI":"10.1016\/j.virol.2016.12.012","article-title":"Ebola virus VP35 blocks stress granule assembly.","volume":"502","author":"V Le Sage","year":"2017","journal-title":"Virology."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"48","DOI":"10.12688\/f1000research.6164.2","article-title":"FDA approved drugs as potential Ebola treatments [version 2; peer review: 2 approved].","volume":"4","author":"S Ekins","year":"2015","journal-title":"F1000Res."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"285-6","DOI":"10.1055\/s-2006-957883","article-title":"The effect of some 2-substituted quinolines isolated from Galipea longiflora on Plasmodium vinckei petteri infected mice.","volume":"62","author":"J Gantier","year":"1996","journal-title":"Planta Med."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/9-268\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/9-268\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/9-268\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T07:20:12Z","timestamp":1591082412000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/9-268\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,17]]},"references-count":33,"URL":"https:\/\/doi.org\/10.12688\/f1000research.22352.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.24661.r64097","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.24661.r62501","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.24661.r62501","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.24661.r64097","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,17]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/9-268\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.24661.r62501, Veljko Veljkovic, Biomed Protection, Galveston, TX, USA, 27 May 2020, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-268\/v1#referee-response-62501","order":0,"name":"referee-response-62501","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.24661.r64097, Jonas \u0160arlauskas, Department of Xenobiotics Biochemistry, Institute of Biochemistry, Vilnius University, Vilnius, Lithuania, 02 Jun 2020, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-268\/v1#referee-response-64097","order":1,"name":"referee-response-64097","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"SDSM is a recipient of the Vanier CGS D and Canadian Blood Services GFP graduate awards. DRB is partially funded through support provided by Health Canada, but the views expressed herein to not necessarily represent the view of the federal government of Canada.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}