1932

Abstract

Despite the unprecedented Ebola virus outbreak response in West Africa, no Ebola medical countermeasures have been approved by the US Food and Drug Administration. However, multiple valuable lessons have been learned about the conduct of clinical research in a resource-poor, high risk–pathogen setting. Numerous therapeutics were explored or developed during the outbreak, including repurposed drugs, nucleoside and nucleotide analogues (BCX4430, brincidofovir, favipiravir, and GS-5734), nucleic acid–based drugs (TKM-Ebola and AVI-7537), and immunotherapeutics (convalescent plasma and ZMapp). We review Ebola therapeutics progress in the aftermath of the West Africa Ebola virus outbreak and attempt to offer a glimpse of a path forward.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-010716-105055
2017-01-06
2024-06-22
Loading full text...

Full text loading...

/deliver/fulltext/pharmtox/57/1/annurev-pharmtox-010716-105055.html?itemId=/content/journals/10.1146/annurev-pharmtox-010716-105055&mimeType=html&fmt=ahah

Literature Cited

  1. 1. Merriam-Webster.com 2016. Cure Accessed on Mar. 1. http://www.merriam-webster.com/dictionary/cure [Google Scholar]
  2. Greenwood B. 2.  2014. The contribution of vaccination to global health: past, present and future. Philos. Trans. R. Soc. B 369:20130433 [Google Scholar]
  3. Mariner JC, House JA, Mebus CA, Sollod AE, Chibeu D. 3.  et al. 2012. Rinderpest eradication: appropriate technology and social innovations. Science 337:1309–12 [Google Scholar]
  4. Ohimain EI. 4.  2016. Recent advances in the development of vaccines for Ebola virus disease. Virus Res 211:174–85 [Google Scholar]
  5. Sridhar S. 5.  2015. Clinical development of Ebola vaccines. Ther. Adv. Vaccines 3:125–38 [Google Scholar]
  6. 6. WHO (World Health Organ.) 2015. Table of drug clinical trials WHO, Geneva. Accessed on July 23. http://www.who.int/medicines/ebola-treatment/ebola_drug_clinicaltrials/en/ [Google Scholar]
  7. Hensley LE, Dyall J, Olinger GG Jr., Jahrling PB. 7.  2015. Lack of effect of lamivudine on Ebola virus replication. Emerg. Infect. Dis. 21:550–52 [Google Scholar]
  8. Fedson DS. 8.  2015. Immunomodulatory adjunctive treatment options for Ebola virus disease patients: another view. Intensive Care Med. 41:1383 [Google Scholar]
  9. Fedson DS, Jacobson JR, Rordam OM, Opal SM. 9.  2015. Treating the host response to Ebola virus disease with generic statins and angiotensin receptor blockers. mBio 6:e00716 [Google Scholar]
  10. Fedson DS, Rordam OM. 10.  2015. Treating Ebola patients: a ‘bottom up’ approach using generic statins and angiotensin receptor blockers. Int. J. Infect. Dis. 36:80–84 [Google Scholar]
  11. 11. WHO (World Health Organ.) 2015. Categorization and prioritization of drugs for consideration for testing or use in patients infected with Ebola News Release, Jan. 19. Accessed on July 23. http://www.who.int/medicines/ebola-treatment/cat_prioritization_drugs_testing/en/ [Google Scholar]
  12. Bavari S, Bosio CM, Wiegand E, Ruthel G, Will AB. 12.  et al. 2002. Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses. J. Exp. Med. 195:593–602 [Google Scholar]
  13. Bhattacharyya S, Warfield KL, Ruthel G, Bavari S, Aman MJ, Hope TJ. 13.  2010. Ebola virus uses clathrin-mediated endocytosis as an entry pathway. Virology 401:18–28 [Google Scholar]
  14. Madrid PB, Chopra S, Manger ID, Gilfillan L, Keepers TR. 14.  et al. 2013. A systematic screen of FDA-approved drugs for inhibitors of biological threat agents. PLOS ONE 8:e60579 [Google Scholar]
  15. Miller ME, Adhikary S, Kolokoltsov AA, Davey RA. 15.  2012. Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection. J. Virol. 86:7473–83 [Google Scholar]
  16. Sakurai Y, Kolokoltsov AA, Chen CC, Tidwell MW, Bauta WE. 16.  et al. 2015. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment. Science 347:995–98 [Google Scholar]
  17. Yonezawa A, Cavrois M, Greene WC. 17.  2005. Studies of Ebola virus glycoprotein-mediated entry and fusion by using pseudotyped human immunodeficiency virus type 1 virions: involvement of cytoskeletal proteins and enhancement by tumor necrosis factor alpha. J. Virol. 79:918–26 [Google Scholar]
  18. Cheng H, Lear-Rooney CM, Johansen L, Varhegyi E, Chen ZW. 18.  et al. 2015. Inhibition of Ebola and Marburg viral entry by G protein-coupled receptor antagonists. J. Virol. 89:9932–38 [Google Scholar]
  19. Johansen LM, DeWald LE, Shoemaker CJ, Hoffstrom BG, Lear-Rooney CM. 19.  et al. 2015. A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity. Sci. Trans. Med. 7:290ra89 [Google Scholar]
  20. Johansen LM, Brannan JM, Delos SE, Shoemaker CJ, Stossel A. 20.  et al. 2013. FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection. Sci. Transl. Med. 5:190ra79 [Google Scholar]
  21. Gehring G, Rohrmann K, Atenchong N, Mittler E, Becker S. 21.  et al. 2014. The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry. J. Antimicrob. Chemother. 69:2123–31 [Google Scholar]
  22. Salata C, Baritussio A, Munegato D, Calistri A, Ha HR. 22.  et al. 2015. Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process. Pathog. Dis. 73:ftv032 [Google Scholar]
  23. Turone F. 23.  2014. Doctors trial amiodarone for Ebola in Sierra Leone. BMJ 349:g7198 [Google Scholar]
  24. Makimoto H, Noda T, Kurita T, Nakajima I, Yokoyama T. 24.  et al. 2011. Incessant monomorphic ventricular tachycardia induced by the proarrhythmic effect of amiodarone. Intern. Med. 50:2591–95 [Google Scholar]
  25. Chow MS. 25.  1996. Intravenous amiodarone: pharmacology, pharmacokinetics, and clinical use. Ann. Pharmacother. 30:637–43 [Google Scholar]
  26. Epstein AE, Olshansky B, Naccarelli GV, Kennedy JI Jr., Murphy EJ, Goldschlager N. 26.  2015. Practical management guide for clinicians who treat patients with amiodarone. Am. J. Med. 129:468–75 [Google Scholar]
  27. Vorperian VR, Havighurst TC, Miller S, January CT. 27.  1997. Adverse effects of low dose amiodarone: a meta-analysis. J. Am. Coll. Cardiol. 30:791–98 [Google Scholar]
  28. Gignoux E, Azman AS, de Smet M, Azuma P, Massaquoi M. 30.  et al. 2016. Effect of artesunate-amodiaquine on mortality related to Ebola virus disease. N. Engl. J. Med. 374:23–32 [Google Scholar]
  29. Deville-Bonne D, El Amri C, Meyer P, Chen Y, Agrofoglio LA, Janin J. 28.  2010. Human and viral nucleoside/nucleotide kinases involved in antiviral drug activation: structural and catalytic properties. Antiviral Res 86:101–20 [Google Scholar]
  30. Jordheim LP, Durantel D, Zoulim F, Dumontet C. 29.  2013. Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat. Rev. Drug Discov. 12:447–64 [Google Scholar]
  31. Warren TK, Wells J, Panchal RG, Stuthman KS, Garza NL. 31.  et al. 2014. Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature 508:402–5 [Google Scholar]
  32. 32. Biocryst Pharm 2014. BioCryst announces study results for BCX4430 in a non-human primate model of Ebola virus infection News Release, Dec. 23. Accessed on Mar. 20, 2016. http://investor.shareholder.com/biocryst/releasedetail.cfm?ReleaseID=888802 [Google Scholar]
  33. 33. ClinicalTrials.gov 2016. A Phase 1 study to evaluate the safety, tolerability and pharmacokinetics of BCX4430 NCT02319772, US Natl. Inst. Health, Bethesda, MD. https://clinicaltrials.gov/ct2/show/NCT02319772 [Google Scholar]
  34. Hostetler KY. 34.  2010. Synthesis and early development of hexadecyloxypropylcidofovir: an oral anti-poxvirus nucleoside phosphonate. Viruses 2:2213–25 [Google Scholar]
  35. Lanier R, Trost L, Tippin T, Lampert B, Robertson A. 35.  et al. 2010. Development of CMX001 for the treatment of poxvirus infections. Viruses 2:2740–62 [Google Scholar]
  36. 36. Chimerix, Inc 2014. Chimerix announces emergency investigational new drug applications for brincidofovir authorized by FDA for patients with Ebola virus disease News Release, Oct. 6. Accessed on Oct. 11, 2015. http://ir.chimerix.com/releasedetail.cfm?releaseid=874647 [Google Scholar]
  37. McMullan LK, Flint M, Dyall J, Albarino C, Olinger GG. 37.  et al. 2016. The lipid moiety of brincidofovir is required for in vitro antiviral activity against Ebola virus. Antivir. Res. 125:71–78 [Google Scholar]
  38. 38. ClinicalTrials.gov 2016. Phase III, open-labeled, multicenter study of the safety and efficacy of brincidofovir (CMX001) in the treatment of early versus late adenovirus infection NCT02087306, US Natl. Inst. Health, Bethesda, MD. http://clinicaltrials.gov/show/NCT02087306 [Google Scholar]
  39. Marty FM, Winston DJ, Rowley SD, Vance E, Papanicolaou GA. 39.  et al. 2013. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N. Engl. J. Med. 369:1227–36 [Google Scholar]
  40. Painter W, Robertson A, Trost LC, Godkin S, Lampert B, Painter G. 40.  2012. First pharmacokinetic and safety study in humans of the novel lipid antiviral conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA viruses. Antimicrob. Agents Chemother. 56:2726–34 [Google Scholar]
  41. Florescu DF, Kalil AC, Hewlett AL, Schuh AJ, Stroher U. 41.  et al. 2015. Administration of brincidofovir and convalescent plasma in a patient with Ebola virus disease. Clin. Infect. Dis. 61:969–73 [Google Scholar]
  42. 42. Emory Healthc 2014. Care of the Patient with Ebola Virus Disease. Atlanta: Emory Healthc Accessed on Oct. 11, 2015. http://www.emoryhealthcare.org/ebola-protocol/pdf/overview-of-ebola.pdf [Google Scholar]
  43. Cohen J, Enserink M. 43.  2016. As Ebola epidemic draws to a close, a thin scientific harvest. Science 351:12–13 [Google Scholar]
  44. 44. Chimerix, Inc 2015. Brincidofovir will not be considered in further clinical trials in Ebola virus disease News Release, Jan. 30. Accessed on Oct. 11. http://ir.chimerix.com/releasedetail.cfm?releaseid=893927 [Google Scholar]
  45. Furuta Y, Takahashi K, Fukuda Y, Kuno M, Kamiyama T. 45.  et al. 2002. In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob. Agents Chemother. 46:977–81 [Google Scholar]
  46. Baranovich T, Wong SS, Armstrong J, Marjuki H, Webby RJ. 46.  et al. 2013. T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J. Virol. 87:3741–51 [Google Scholar]
  47. Sangawa H, Komeno T, Nishikawa H, Yoshida A, Takahashi K. 47.  et al. 2013. Mechanism of action of T-705 ribosyl triphosphate against influenza virus RNA polymerase. Antimicrob. Agents Chemother. 57:5202–8 [Google Scholar]
  48. Caroline AL, Powell DS, Bethel LM, Oury TD, Reed DS, Hartman AL. 48.  2014. Broad spectrum antiviral activity of favipiravir (T-705): protection from highly lethal inhalational Rift Valley Fever. PLOS Negl. Trop. Dis. 8:e2790 [Google Scholar]
  49. Gowen BB, Smee DF, Wong MH, Hall JO, Jung KH. 49.  et al. 2008. Treatment of late stage disease in a model of arenaviral hemorrhagic fever: T-705 efficacy and reduced toxicity suggests an alternative to ribavirin. PLOS ONE 3:e3725 [Google Scholar]
  50. Gowen BB, Wong MH, Jung KH, Sanders AB, Mendenhall M. 50.  et al. 2007. In vitro and in vivo activities of T-705 against arenavirus and bunyavirus infections. Antimicrob. Agents Chemother. 51:3168–76 [Google Scholar]
  51. Gowen BB, Wong MH, Jung KH, Smee DF, Morrey JD, Furuta Y. 51.  2010. Efficacy of favipiravir (T-705) and T-1106 pyrazine derivatives in phlebovirus disease models. Antivir. Res. 86:121–27 [Google Scholar]
  52. Julander JG, Shafer K, Smee DF, Morrey JD, Furuta Y. 52.  2009. Activity of T-705 in a hamster model of yellow fever virus infection in comparison with that of a chemically related compound, T-1106. Antimicrob. Agents Chemother. 53:202–9 [Google Scholar]
  53. Nyakatura EK, Frei JC, Lai JR. 53.  2015. Chemical and structural aspects of Ebola virus entry inhibitors. ACS Infect. Dis. 1:42–52 [Google Scholar]
  54. Rocha-Pereira J, Jochmans D, Dallmeier K, Leyssen P, Nascimento MS, Neyts J. 54.  2012. Favipiravir (T-705) inhibits in vitro norovirus replication. Biochem. Biophys. Res. Commun. 424:777–80 [Google Scholar]
  55. Smither SJ, Eastaugh LS, Steward JA, Nelson M, Lenk RP, Lever MS. 55.  2014. Post-exposure efficacy of oral T-705 (favipiravir) against inhalational Ebola virus infection in a mouse model. Antivir. Res. 104:153–55 [Google Scholar]
  56. Oestereich L, Ludtke A, Wurr S, Rieger T, Munoz-Fontela C, Gunther S. 56.  2014. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antivir. Res. 105:17–21 [Google Scholar]
  57. Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. 57.  2013. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antivir. Res. 100:446–54 [Google Scholar]
  58. Cardile AP, Mayers DL, Bavari S. 58.  2014. Current status of chemically synthesized inhibitors of Ebola virus. Recent Pat. Anti-Infect. Drug Discov. 9:97–103 [Google Scholar]
  59. Wolf T, Kann G, Becker S, Stephan C, Brodt HR. 59.  et al. 2015. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet 385:1428–35 [Google Scholar]
  60. 60. Fujifilm Corp 2014. Avigan®Tablet 200mg administered to a French woman infected with Ebola virus News Release, Sept. 26. Accessed on Oct. 11, 2015. http://www.fujifilm.com/news/n140926.html [Google Scholar]
  61. Varkey JB, Shantha JG, Crozier I, Kraft CS, Lyon GM. 61.  et al. 2015. Persistence of Ebola virus in ocular fluid during convalescence. N. Engl. J. Med. 372:2423–27 [Google Scholar]
  62. Mora-Rillo M, Arsuaga M, Ramirez-Olivencia G, de la Calle F, Borobia AM. 62.  et al. 2015. Acute respiratory distress syndrome after convalescent plasma use: treatment of a patient with Ebola virus disease contracted in Madrid, Spain. Lancet Respir. Med. 3:554–62 [Google Scholar]
  63. Sissoko D, Laouenan C, Folkesson E, M'Lebing AB, Beavogui AH. 63.  et al. 2016. Experimental treatment with favipiravir for Ebola virus disease (the JIKI Trial): a historically controlled, single-arm proof-of-concept trial in Guinea. PLOS Med. 13:e1001967 [Google Scholar]
  64. Sissoko D, Anglaret X, Malvy D. 64.  2015. Favipiravir in patients with Ebola virus disease: early results of the JIKI trial in Guinea. Proc. Conf. Retrovir. Opportunistic Infect., Seattle, WA, Feb. 23–26 Abstr. 103-ALB [Google Scholar]
  65. Mentré F, Taburet AM, Guedj J, Anglaret X, Keïta S. 65.  et al. 2015. Dose regimen of favipiravir for Ebola virus disease. Lancet Infect. Dis. 15:150–51 [Google Scholar]
  66. Bouazza N, Treluyer JM, Foissac F, Mentré F, Taburet AM. 66.  et al. 2015. Favipiravir for children with Ebola. Lancet 385:603–4 [Google Scholar]
  67. 67. Panel Antiretrovir. Guidel. Adults Adolesc 2016. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Rep., Dep. Health Hum. Serv., Washington, D.C. Accessed on Mar. 2. http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf [Google Scholar]
  68. Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL. 68.  et al. 2016. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature 531:381–85 [Google Scholar]
  69. 69. Gilead 2016. Gilead Pipeline Foster City, CA: Gilead. Accessed on Mar 5 http://www.gilead.com/research/pipeline [Google Scholar]
  70. Jacobs M, Rodger A, Bell DJ, Bhagani S, Cropley I. 70.  et al. 2016. Late Ebola virus relapse causing meningoencephalitis: a case report. Lancet 388:498–503 [Google Scholar]
  71. Farge E. 71.  2015. Guinea's last Ebola case, a baby girl, leaves hospital. Reuters Nov. 28. Accessed on Mar. 5, 2016. http://www.reuters.com/article/us-health-ebola-guinea-idUSKBN0TH0PB20151128 [Google Scholar]
  72. Kole R, Krainer AR, Altman S. 72.  2012. RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nat. Rev. Drug Discov. 11:125–40 [Google Scholar]
  73. Spurgers KB, Sharkey CM, Warfield KL, Bavari S. 73.  2008. Oligonucleotide antiviral therapeutics: antisense and RNA interference for highly pathogenic RNA viruses. Antivir. Res. 78:26–36 [Google Scholar]
  74. Cullen BR. 74.  2014. Viruses and RNA interference: issues and controversies. J. Virol. 88:12934–36 [Google Scholar]
  75. Friedrich BM, Trefry JC, Biggins JE, Hensley LE, Honko AN. 75.  et al. 2012. Potential vaccines and post-exposure treatments for filovirus infections. Viruses 4:1619–50 [Google Scholar]
  76. Torrecilla J, Rodríguez-Gascón A, Solinís MA, del Pozo-Rodríguez A. 76.  2014. Lipid nanoparticles as carriers for RNAi against viral infections: current status and future perspectives. BioMed. Res. Int. 2014:161794 [Google Scholar]
  77. Geisbert TW, Lee AC, Robbins M, Geisbert JB, Honko AN. 77.  et al. 2010. Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study. Lancet 375:1896–905 [Google Scholar]
  78. Thi EP, Mire CE, Lee AC, Geisbert JB, Zhou JZ. 78.  et al. 2015. Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates. Nature 521:362–65 [Google Scholar]
  79. Iversen PL, Warren TK, Wells JB, Garza NL, Mourich DV. 79.  et al. 2012. Discovery and early development of AVI-7537 and AVI-7288 for the treatment of Ebola virus and Marburg virus infections. Viruses 4:2806–30 [Google Scholar]
  80. Warren TK, Warfield KL, Wells J, Swenson DL, Donner KS. 80.  et al. 2010. Advanced antisense therapies for postexposure protection against lethal filovirus infections. Nat. Med. 16:991–94 [Google Scholar]
  81. Warren TK, Whitehouse CA, Wells J, Welch L, Heald AE. 81.  et al. 2015. A single phosphorodiamidate morpholino oligomer targeting VP24 protects rhesus monkeys against lethal Ebola virus infection. mBio 6:e02344–14 [Google Scholar]
  82. Kugelman JR, Sanchez-Lockhart M, Andersen KG, Gire S, Park DJ. 82.  et al. 2015. Evaluation of the potential impact of Ebola virus genomic drift on the efficacy of sequence-based candidate therapeutics. mBio 6:e02227–14 [Google Scholar]
  83. Shurtleff AC, Whitehouse CA, Ward MD, Cazares LH, Bavari S. 83.  2015. Pre-symptomatic diagnosis and treatment of filovirus diseases. Front. Microbiol. 6:108 [Google Scholar]
  84. Heald AE, Iversen PL, Saoud JB, Sazani P, Charleston JS. 84.  et al. 2014. Safety and pharmacokinetic profiles of phosphorodiamidate morpholino oligomers with activity against Ebola virus and Marburg virus: results of two single-ascending-dose studies. Antimicrob. Agents Chemother. 58:6639–47 [Google Scholar]
  85. Dunning J, Sahr F, Rojek A, Gannon F, Carson G. 85.  et al. 2016. Experimental treatment of Ebola virus disease with TKM-130803: a single-arm Phase 2 clinical trial. PLOS Med 13:e1001997 [Google Scholar]
  86. 86. Tekmira 2015. Tekmira provides update on TKM-Ebola-Guinea News Release, June 19. Accessed on July 23. http://investor.tekmirapharm.com/releasedetail.cfm?ReleaseID=918694 [Google Scholar]
  87. 87. Tekmira 2015. Tekmira announces launch of Arbutus Biopharma, a Hepatitis B solutions company New Release, July 20. Accessed on Mar. 5, 2016. http://investor.arbutusbio.com/releasedetail.cfm?ReleaseID=922758 [Google Scholar]
  88. Mupapa K, Massamba M, Kibadi K, Kuvula K, Bwaka A. 88.  et al. 1999. Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. J. Infect. Dis. 179:Suppl. 1S18–23 [Google Scholar]
  89. Colebunders RL, Cannon RO. 89.  2015. Large-scale convalescent blood and plasma transfusion therapy for Ebola virus disease. J. Infect. Dis. 211:1208–10 [Google Scholar]
  90. van Griensven J, Edwards T, de Lamballerie X, Semple MG, Gallian P. 90.  et al. 2016. Evaluation of convalescent plasma for Ebola virus disease in Guinea. N. Engl. J. Med. 374:33–42 [Google Scholar]
  91. Jahrling PB, Geisbert J, Swearengen JR, Jaax GP, Lewis T. 91.  et al. 1996. Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses. Arch. Virol. Suppl. 11:135–40 [Google Scholar]
  92. Jahrling PB, Geisbert JB, Swearengen JR, Larsen T, Geisbert TW. 92.  2007. Ebola hemorrhagic fever: evaluation of passive immunotherapy in nonhuman primates. J. Infect. Dis. 196:Suppl. 2S400–3 [Google Scholar]
  93. Jahrling PB, Geisbert TW, Geisbert JB, Swearengen JR, Bray M. 93.  et al. 1999. Evaluation of immune globulin and recombinant interferon-α2b for treatment of experimental Ebola virus infections. J. Infect. Dis. 179:Suppl. 1S224–34 [Google Scholar]
  94. Kudoyarova-Zubavichene NM, Sergeyev NN, Chepurnov AA, Netesov SV. 94.  1999. Preparation and use of hyperimmune serum for prophylaxis and therapy of Ebola virus infections. J. Infect. Dis. 179:Suppl. 1S218–23 [Google Scholar]
  95. Dye JM, Herbert AS, Kuehne AI, Barth JF, Muhammad MA. 95.  et al. 2012. Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease. PNAS 109:5034–39 [Google Scholar]
  96. Lyon GM, Mehta AK, Varkey JB, Brantly K, Plyler L. 96.  et al. 2014. Clinical care of two patients with Ebola virus disease in the United States. N. Engl. J. Med. 371:2402–9 [Google Scholar]
  97. Qiu X, Wong G, Audet J, Bello A, Fernando L. 97.  et al. 2014. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 514:47–53 [Google Scholar]
  98. Mendoza EJ, Qiu X, Kobinger GP. 98.  2016. Progression of Ebola therapeutics during the 2014–2015 outbreak. Trends Mol. Med. 22:164–73 [Google Scholar]
  99. Davey R. 99.  2016. PREVAIL II: a randomized controlled trial of ZMappin acute Ebola virus infection Webcast, CROI, Feb. 22–25. Accessed on Mar. 10. http://www.croiwebcasts.org/console/player/29572?mediaType=audio& [Google Scholar]
  100. Corti D, Misasi J, Mulangu S, Stanley DA, Kanekiyo M. 100.  et al. 2016. Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Science 351:1339–42 [Google Scholar]
  101. Holtsberg FW, Shulenin S, Vu H, Howell KA, Patel SJ. 101.  et al. 2015. Pan-ebolavirus and pan-filovirus mouse monoclonal antibodies: protection against Ebola and Sudan viruses. J. Virol. 90:266–78 [Google Scholar]
  102. Furuyama W, Marzi A, Nanbo A, Haddock E, Maruyama J. 102.  et al. 2016. Discovery of an antibody for pan-ebolavirus therapy. Sci. Rep. 6:20514 [Google Scholar]
  103. Howell KA, Qiu X, Brannan JM, Bryan C, Davidson E. 103.  et al. 2016. Antibody treatment of Ebola and Sudan virus infection via a uniquely exposed epitope within the glycoprotein receptor-binding site. Cell Rep. 15:1514–26 [Google Scholar]
  104. Qiu X, Audet J, Lv M, He S, Wong G. 104.  et al. 2016. Two-mAb cocktail protects macaques against the Makona variant of Ebola virus. Sci. Transl. Med. 8:329ra33 [Google Scholar]
  105. Smith LM, Hensley LE, Geisbert TW, Johnson J, Stossel A. 105.  et al. 2013. Interferon-β therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever. J. Infect. Dis. 208:310–18 [Google Scholar]
  106. Adebamowo C, Bah-Sow O, Binka F, Bruzzone R, Caplan A. 106.  et al. 2014. Randomised controlled trials for Ebola: practical and ethical issues. Lancet 384:1423–24 [Google Scholar]
  107. 107. Pres. Comm. Study Bioethical Issues 2015. Ethics and Ebola: Public Health Planning and Response. Rep., Pres. Comm. Study Bioethical Issues, Washington, DC. Accessed on Mar. 20, 2016. http://bioethics.gov/sites/default/files/Ethics-and-Ebola_PCSBI_508.pdf [Google Scholar]
  108. Dodd LE, Proschan MA, Neuhaus J, Koopmeiners JS, Neaton J. 108.  et al. 2016. Design of a randomized controlled trial for Ebola virus disease medical countermeasures: PREVAIL II, the Ebola MCM study. J. Infect. Dis. 213:1906–13 [Google Scholar]
/content/journals/10.1146/annurev-pharmtox-010716-105055
Loading
/content/journals/10.1146/annurev-pharmtox-010716-105055
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error