Research on prevention and treatment of hemorrhagic fevers
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Biological Threats Identification and Countermeasure Centre, Military Institute of Hygiene and Epidemiology, Puławy, Poland
Military Institute of Hygiene and Epidemiology, Warsaw, Poland
Department of Epidemiology, Medical University, Warsaw, Poland
Ann Agric Environ Med 2012;19(2):165–171
Viral hemorrhagic fevers are severe zoonotic diseases caused by RNA-viruses classified into 4 families: Arenaviridae, Bunyaviridae, Filoviridae, and Flaviviridae. They are present on all continents except Antarctica, their person-to-person spread is easy, and there is a high risk of them being used as weapon by bioterrorists. So far, efforts to develop effective drugs against these viruses have failed, and typical therapy usually relies on symptomatic treatment. Search for substances that could effectively inhibit this type of infections is now a priority. The presented paper gives an overview of different approaches used in combating the viral hemorrhagic fevers. Researchers look for safe antiviral agents with appropriate properties among natural sources, such as various types of herbs plants, algae, or essential oils obtained from trees, as well as investigate the use of various synthetic substances. The aim is to broaden the pool of available antiviral drugs that could replace hitherto applied medicines such as ribavirin, which is not always sufficiently effective and may have side-effects. The scientists focus not only on combating the diseases, but also on their prevention. For this purpose, recombinant vaccines or various types of immunomodulators may serve as a useful tools. Results of the latest studies are promising and encourage further work which may eventually lead to the solution of the urgent problem of hemorrhagic fevers.
Justyna Joniec   
Biological Threats Identification and Countermeasure Centre, Military Institute of Hygiene and Epidemiology, Puławy, Poland
1. Geisbert T W, Lee ACH, Robbins M, Geisbert JB, Honko AN, Sood V et al. Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study. Lancet 2010; 375: 1896-905.
2. (access: 2011.09.27).
3. (access: 2011.09.27).
4. (access: 2011.09.27).
5. (access: 2011.09.27).
6. (access: 2011.09.27).
7. Mirski T, Bartoszcze M, Bielawska-Drózd A. Globalizacja a choroby zakaźne. Przegl Epidemiol 2011;65(4):651-658.
8. Woodrow CJ, Eziefula AC, Agranioff D, Scott GM, Watson J, Chiodini PL et al. Early risk assessment for viral haemorrhagic fever: experience at the Hospital for tropical diseases. J Infection. 2007; 54: 6-11.
9. Borio L, Inglesby T, Peters CJ, Alan L, Schmaljohn L, James MH et al. Hemorrhagic fever viruses as biological weapons medical and public health management. JAMA 2002; 287(18): 2391-2405.
10. Talarico LB, Pujol CA, Zibetti RGM, Faria PCS, Noseda MD, Duarte MER et al. The antiviral activity of sulfated polysaccharides against dengue virus is dependent on virus serotype and host cell. Antivir Res. 2005; 66: 103-110.
11. Ono L, Wollinger W, Rocco IM, Combra TLM, Gorin PAJ, Sierakowski MR. In vitro and in vivo antiviral properties of sulfated galactomannans against yellow fever virus (BeH111 strain) and dengue 1 virus (Hawaii strain). Antivir Res. 2003; 60: 201-208.
12. Michelow IC, Dong M, MungalL BA, Michael Yantosca L, Lear C, Ji X et al. A novel l-ficoli/mannose-binding lecithin chimeric molecule with anhanced activity against Ebola virus. J Biol Chem. 2010; 285(32): 24729-24739.
13. Jain M, Ganju L, Katiyal A, Padwad Y., Mishra KP, Chanda S et al. Effect of Hippophae rhamnoides leaf extract against Dengue virus infection in human blood-derived macrophages. Phytomedicine. 2008; 15: 793-799.
14. Reis SRIN, Valente LMM, Sampaio AL, Siani AC, Gandini M, Azeredo EL et al. Immunomodulating and antiviral activities of Uncariatomentosa on human monocytes infected with Dengue Virus-2. Int Immunopharmacol. 2008; 8: 468-476.
15. Heitzman ME, Neto CC, Winiarz E, Veisberg AJ, Hammond GB. Ethnobotany, phytochemistry and pharmacology of Uncaria (Rubiaceae). Phytochemistry. 2005; 66: 5-29.
16. Valente L. M. M. Cat’s claw [Uncaria tomentosa (Willd.) DC. and Uncaria guianensis (Aubl.) Gmel.]: an overview of their more relevant aspects. Fitos. 2006; 2: 48-58.
17. Liu Y, Yang Z, Deng H, Xiao H, Qu Ch. Separation and Anti-Hantaan Virus Activity of Extracts from Alternanthera philoxcroides in vitro and in vivo. Wuhan University J Nat Sci. 2007; 12(6): 1143-1147.
18. Meneses R, Ocazionez RE, Martinez JR, Stashenko EE. Inhibitory effect of essential oils obtained from plants grown in Colombia on yellow fever virus replication in vitro. ACMAs 2009; 8(8): 1-6.
19. Candurra NA, Maskin L, Damonte EB. Inhibition of arenavirus in vitro by phenotiazines. Antivil Res. 1996; 31: 149-158.
20. Chung D-H, Strouse JJ, Sun Y, Arterburn JB, Parker WB,Jonsson CB. Synthesis and anti-Hantaan virus activity of N1- 3-fluorophenyl-inosine. Antivir Res. 2009; 83: 80-85.
21. Bray M, Paragas J. Experimental therapy of filovirus infections. Antivir Res. 2002; 54: 1-17.
22. Bray M, Driscoll J, Huggins JW. Treatment of lethal Ebola virus infection in mice with a single dose of an S-adenosyl-L-homocysteine hydrolase inhibitor. Antivir Res. 2000; 45: 135-147.
23. Yermolina MV, Wang J, Caffrey M, Rong LL, Wardrop DJ. Discovery, synthesis, and biological evaluation of a novel group of selective inhibitors of filoviral entry. J Med Chem. 2011; 54(3): 765-781.
24. Simon M, Falk KI, Lundkvist Å, Mirazimi A. Exogenous nitric oxide inhibits Crimean Congo hemorrhagic fever virus. Virus Res. 2006; 120: 184-190.
25. Barrientos LG, O’Keefe BR, Bray M, Sanchez A, Gronenborn AM, Boyd MR. Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus. Antivir Res. 2003; 58: 47-56.
26. Aman MJ, Kinch MS, Warfield K, Warren T, Yunus A, Enterlein S et al. Development of a broad-spectrum antiviral with activity against Ebola virus. Antivir Res. 2009; 83: 245-251.
27. Bouloy M, Flick R. Reverse genetics technology for Rift Valley fever virus: Current and future applications for the development of therapeutics and vaccines. Antivir Res. 2009; 84: 101-118.
28. Barradas JS, Errea MI, D’Accorso NB, Sepúlveda CS, Damonte EB. Imidazo [2,1-b] thiazole carbohydrate derivatives: Synthesis and antiviral activity against Junin virus, agent of Argentine hemorrhagic fever. Eur J Med Chem. 2011; 46: 259-264.
29. Smith DR, McCarthy S, Chrovian A, Olinger G, Stossel A, Geisbert TW et al. Inhibition of heat-shock protein 90 reduces Ebola virus replication. Antivir Res. 2010; 87: 187-194.
30. Kato D, Era S, Watanabe I, Arihara M, Sugiera N, Kimata K et al. Antiviral activity of chondroitin sulphate E targeting dengue virus envelope protein. Antivir Res. 2010; 88: 236-243.
31. Sepúlveda CS, Fascio ML, Mazzucco MB, Palacios MLD, Pellón RF, Garcia CC et all. Synthesis and evaluation of N-substituted acridones as antiviral agent against haemorrhagic fever viruses. Antivir Chem Chemoth. 2008; 19: 41-47.
32. Deng H, Luo F, Zhong Q, Liu Y, Yang Z. Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro. Acta Pharm Sinic. 2009; 30: 1015-1024.
33. Delogu I, Pastorino B, Baronti C, Neugairėde A, Bonnet E, de Lamballerie X. In vitro antiviral activity of arbidol against Chikungunya virus and characteristics of a selected resistant mutant. Antivir Res. 2011; 90: 99-107.
34. Maves RC, Oré R, MC, Porter KR, Kochel TJ. Immunogenicity and protective efficacy of a psoralen-inactivated dengue-1 virus vaccine candidate in Aotus nancymaae monkeys. Vaccine. 2011; 29: 2691-2696.
35. Näslund J, Lagerqvist N, Habjan M, Lundkvist Å, Evander M, Ahlm C et al. Vaccination with virus-like particles protects mice from lethal infection of Rift Valley Fever Virus. Virology. 2009; 385: 409-415.
36. Mandell RB, Kaukuntla R, Mogler LJK, Carzoli AK, Freiberg AN, Holbrook MR et al. A replication-incompetent Rift Valley fever vaccine: Chimeric virus-like particles protect mice and rats against lethal challenge. Virology 2010; 397: 187-198.
37. Rao M, Matyas GR, Griedar F, Anderson K, Jahrling PB, Alving CR. Cytotoxic T lymphocytes to Ebola Zaire virus are induced in mice by immunization with liposomes containing lipid A. Vaccine. 1997; 17: 2991-2998.
38. Sun J, DuFort Ch, Daniel M-Ch, Murali A, Chen Ch, Gopinath K, Stein B et al. Core-controlled polymorphism in virus-like particles. PNAS 2007; 104(4): 1354-1359.
39. Yang CE, Ye L, Compans RW: Protection against filoviruses infection: virus particle vaccines. Expert Rev Vacc. 2008; 79, 333-344.
40. Sun Y, Carrion R, Ye L, Wen Z, Ro Y-T, Brasky K et al. Protection against lethal challenge by Ebola virus-like particles produced in insect cells. Virology. 2009; 383: 12-21.
41. Daddario-DiCaprio KM, Geisbert TW, Geisbert JB, Ströher U, Hensley LE, Grolla A et all. Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates: an efficacy assessment. Lancet 2006; 367: 1399-404.
42. Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet 2011; 377: 849-62.
43. Geisbert TW, Hensley LE, Geisnert JB, Leung A, Johnson JC, Grolla A et al. Postexposure treatment of Marburg virus infection. Emerg Infect Dis. 2010; 16(7): 1119-1121.
44. Hensley LE, Malangu S, Asiedu C, Johnson J, Honko AN, Stanley D et al. Demonstration of cross-protective vaccine immunity against an emerging pathogenic Ebolavirus species. PLoS Pathogens 2010; 6(5); e1000904. doi:10.1371/journal.ppat.1000904.
45. Hayes EB. Is it time for a new yellow fever vaccine? Vaccine 2010; 28: 8073-8076.
46. Monath TP, Fowler E, Johnson CT, Balser DOJ, Morin MJ, Sisti M et al. An inactivated cell-culture vaccine against Yellow Fever. N Engl J Med. 2011; 364: 1326-33.
47. Park K, Kim ChS, Moon K-T. Protection effectiveness of Hantavirus vaccine. Emerg Infect Dis. 2004; 10(12): 2218-22020.
48. Geisbert TW, Hensley LE, Kagan E, Yu EZ, Geisbert JB, Daddario-DiCaprio K et al. Postexposure protection of guinea pigs against a lethal Ebola virus challenge is conferred by RNA interference. JID 2006; 193: 1650-1657.
49. Fowler T, Bamberg S, Möller P, Klenk H-D, Meyer TF, Becker S et al. Inhibition of Marburg virus protein expression and viral release by RNA interference. J Gen Virol. 2005; 86: 1181-1188.
50. Enterlein S, Warfield KL, Swenson DL, Stein DA, Smith JL, Gamble SC et al. VP35 knockdown inhibits Ebola virus amplification and protects against lethal infection in mice. Antimicrob Agents Chemother. 2006; 50(30): 984-993.
51. Warren TK, Warfield KL, Wells J, Swenson DL, Donner KS, Van Tongeren SA et al. Advanced antisense therapies for postexposure protection against lethal filovirus infections. Nat Med. 2010; 16(9): 991-994.
52. Takada A, Ebihara H, Jones S, Feldmann H, Kawaoka Y. Protective efficacy of neutralizing antibodies against Ebola virus infection. Vaccine. 2007; 25: 993-999.
53. Lai M, Engle M, Keller T, Johnson S, Gorlatov S, Diamond MS et al. Monoclonal antibody produced in plants efficiently treats West Nile virus infection in mice. PNAS 2010; 107(6): 2419-2424.
54. Miller EH, Harrison JS, Radoshitzky SR, Higgins ChD, Chi X, Kuhn JH et al. Inhibition of Ebola virus entry by a C-peptide targeted to endosomes. J Biol Chem. 2011; 286: 15854-15861.
55. Geisbert TW, Hensley LE, Jahrling PB, Larsen T, Geisbert JB, Paragas J et al. Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet 2003; 362: 1953-58.
56. Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N et al. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 2011; 477: 340-343.
57. Kołodziej M, Joniec J, Bartoszcze M, Mirski T, Gryko R. Peptydy – nowe możliwości zwalczania zakażeń wirusowych (Peptides – a new strategy for combating viral infections). Przegl Epidemiol. 2011; 65: 477-482.