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Open Access 01-12-2016 | Research

Suramin is a potent inhibitor of Chikungunya and Ebola virus cell entry

Authors: Lisa Henß, Simon Beck, Tatjana Weidner, Nadine Biedenkopf, Katja Sliva, Christopher Weber, Stephan Becker, Barbara S. Schnierle

Published in: Virology Journal | Issue 1/2016

Abstract

Background

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes high fever, rash, and recurrent arthritis in humans. It has efficiently adapted to Aedes albopictus, which also inhabits temperate regions and currently causes large outbreaks in the Caribbean and Latin America. Ebola virus (EBOV) is a member of the filovirus family. It causes the Ebola virus disease (EDV), formerly known as Ebola hemorrhagic fever in humans and has a mortality rate of up to 70 %. The last outbreak in Western Africa was the largest in history and has caused approximately 25,000 cases and 10,000 deaths. For both viral infections no specific treatment or licensed vaccine is currently available. The bis-hexasulfonated naphthylurea, suramin, is used as a treatment for trypanosome-caused African river blindness. As a competitive inhibitor of heparin, suramin has been described to have anti-viral activity.

Methods

We tested the activity of suramin during CHIKV or Ebola virus infection, using CHIKV and Ebola envelope glycoprotein pseudotyped lentiviral vectors and wild-type CHIKV and Ebola virus.

Results

Suramin efficiently inhibited CHIKV and Ebola envelope-mediated gene transfer while vesicular stomatitis virus G protein pseudotyped vectors were only marginally affected. In addition, suramin was able to inhibit wild-type CHIKV and Ebola virus replication in vitro. Inhibition occurred at early time points during CHIKV infection.

Conclusion

Suramin, also known as Germanin or Bayer-205, is a market-authorized drug, however shows significant side effects, which probably prevents its use as a CHIKV drug, but due to the high lethality of Ebola virus infections, suramin might be valuable against Ebola infections.

Suhrbier A, Jaffar-Bandjee M-C, Gasque P. Arthritogenic alphaviruses--an overview. Nat Rev Rheumatol. 2012;8:420–9. doi:10.1038/nrrheum.2012.64.CrossRefPubMed

Weaver SC, Osorio JE, Livengood JA, Chen R, Stinchcomb DT. Chikungunya virus and prospects for a vaccine. Expert Rev Vaccines. 2012;11:1087–101. doi:10.1586/erv.12.84.CrossRefPubMedPubMedCentral

Schwartz O, Albert ML. Biology and pathogenesis of chikungunya virus. Nat Rev Microbiol. 2010;8:491–500.CrossRefPubMed

Bajak A. US assesses virus of the Caribbean. Nature. 2014;512:124–5. doi:10.1038/512124a.CrossRefPubMed

Kuehn BM. Chikungunya virus transmission found in the United States: US health authorities brace for wider spread. JAMA. 2014;312:776–7. doi:10.1001/jama.2014.9916.CrossRefPubMed

Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011;377:849–62. doi:10.1016/S0140-6736(10)60667-8.CrossRefPubMedPubMedCentral

Rougeron V, Feldmann H, Grard G, Becker S, Leroy EM. Ebola and Marburg haemorrhagic fever. J Clin Virol. 2015;64:111–9. doi:10.1016/j.jcv.2015.01.014.CrossRefPubMed

Voss JE, Vaney M-C, Duquerroy S, Vonrhein C, Girard-Blanc C, Crublet E, et al. Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography. Nature. 2010;468:709–12. doi:10.1038/nature09555.CrossRefPubMed

Takada A. Filovirus tropism: cellular molecules for viral entry. Front Microbiol. 2012;3:34. doi:10.3389/fmicb.2012.00034.CrossRefPubMedPubMedCentral

10.

Jae LT, Brummelkamp TR. Emerging intracellular receptors for hemorrhagic fever viruses. Trends Microbiol. 2015;23:392–400. doi:10.1016/j.tim.2015.04.006.CrossRefPubMed

11.

Wool-Lewis RJ, Bates P. Characterization of Ebola virus entry by using pseudotyped viruses: identification of receptor-deficient cell lines. J Virol. 1998;72:3155–60.PubMedPubMedCentral

12.

Weber C, Konig R, Niedrig M, Emmerich P, Schnierle BS. A neutralization assay for chikungunya virus infections in a multiplex format. J Virol Methods. 2014;201:7–12. doi:10.1016/j.jviromet.2014.02.001.CrossRefPubMed

13.

Kamhi E, Joo EJ, Dordick JS, Linhardt RJ. Glycosaminoglycans in infectious disease. Biol Rev Camb Philos Soc. 2013;88:928–43. doi:10.1111/brv.12034.CrossRefPubMed

14.

Liu J, Thorp SC. Cell surface heparan sulfate and its roles in assisting viral infections. Med Res Rev. 2002;22:1–25.CrossRefPubMed

15.

Salvador B, Sexton NR, Carrion Jr R, Nunneley J, Patterson JL, Steffen I, et al. Filoviruses utilize glycosaminoglycans for their attachment to target cells. J Virol. 2013;87:3295–304. doi:10.1128/JVI.01621-12.CrossRefPubMedPubMedCentral

16.

O’Hearn A, Wang M, Cheng H, Lear-Rooney CM, Koning K, Rumschlag-Booms E, et al. Role of EXT1 and glycosaminoglycans in the early stage of filovirus entry. J Virol. 2015. doi:10.1128/JVI.03689-14.PubMedPubMedCentral

17.

Silva LA, Khomandiak S, Ashbrook AW, Weller R, Heise MT, Morrison TE, Dermody TS. A single-amino-acid polymorphism in Chikungunya virus E2 glycoprotein influences glycosaminoglycan utilization. J Virol. 2014;88:2385–97. doi:10.1128/JVI.03116-13.CrossRefPubMedPubMedCentral

18.

Mitsuya H, Popovic M, Yarchoan R, Matsushita S, Gallo RC, Broder S. Suramin protection of T cells in vitro against infectivity and cytopathic effect of HTLV-III. Science. 1984;226:172–4.CrossRefPubMed

19.

Yahi N, Sabatier JM, Nickel P, Mabrouk K, Gonzalez-Scarano F, Fantini J. Suramin inhibits binding of the V3 region of HIV-1 envelope glycoprotein gp120 to galactosylceramide, the receptor for HIV-1 gp120 on human colon epithelial cells. J Biol Chem. 1994;269:24349–53.PubMed

20.

Aguilar HC, Anderson WF, Cannon PM. Cytoplasmic tail of Moloney murine leukemia virus envelope protein influences the conformation of the extracellular domain: implications for mechanism of action of the R Peptide. J Virol. 2003;77:1281–91.CrossRefPubMedPubMedCentral

21.

Kessler HA, Pottage JC, Trenholme GM, Benson CA, Levin S. Effects of suramin on in vitro HBsAg production by PLC/PRF/5 cells and hepatitis B virus DNA polymerase activity. AIDS Res. 1986;2:63–72.CrossRefPubMed

22.

Garson JA, Lubach D, Passas J, Whitby K, Grant PR. Suramin blocks hepatitis C binding to human hepatoma cells in vitro. J Med Virol. 1999;57:238–42.CrossRefPubMed

23.

Basavannacharya C, Vasudevan SG. Suramin inhibits helicase activity of NS3 protein of dengue virus in a fluorescence-based high throughput assay format. Biochem Biophys Res Commun. 2014;453:539–44. doi:10.1016/j.bbrc.2014.09.113.CrossRefPubMed

24.

Wang Y, Qing J, Sun Y, Rao Z. Suramin inhibits EV71 infection. Antivir Res. 2014;103:1–6. doi:10.1016/j.antiviral.2013.12.008.CrossRefPubMed

25.

Ellenbecker M, Lanchy J-M, Lodmell JS. Inhibition of Rift Valley fever virus replication and perturbation of nucleocapsid-RNA interactions by suramin. Antimicrob Agents Chemother. 2014;58:7405–15. doi:10.1128/AAC.03595-14.CrossRefPubMedPubMedCentral

26.

Albulescu IC, van Hoolwerff M, Wolters LA, Bottaro E, Nastruzzi C, Yang SC, et al. Suramin inhibits chikungunya virus replication through multiple mechanisms. Antivir Res. 2015;121:39–46. doi:10.1016/j.antiviral.2015.06.013.CrossRefPubMed

27.

Ho Y-J, Wang Y-M, Lu J-W, Wu T-Y, Lin L-I, Kuo S-C, et al. Suramin Inhibits Chikungunya Virus Entry and Transmission. PLoS One. 2015;10:e0133511. doi:10.1371/journal.pone.0133511.CrossRefPubMed

28.

Goffinet C, Schmidt S, Kern C, Oberbremer L, Keppler OT. Endogenous CD317/Tetherin limits replication of HIV-1 and murine leukemia virus in rodent cells and is resistant to antagonists from primate viruses. J Virol. 2010;84:11374–84. doi:10.1128/JVI.01067-10.CrossRefPubMedPubMedCentral

29.

Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D, Naldini L. A third-generation lentivirus vector with a conditional packaging system. J Virol. 1998;72:8463–71.PubMedPubMedCentral

30.

Agarwal S, Nikolai B, Yamaguchi T, Lech P, Somia NV, N1 - Department of Genetics, Cell Biology, and Development, Institute of Human Genetics, University of Minnesota, 420 Delaware Street SE, MMC 206, Minneapolis, MN 55455, USAFAgarwal, Sumit. Construction and use of retroviral vectors encoding the toxic gene barnase. Mol Ther. 2006;14:555–63.CrossRefPubMed

31.

Soneoka Y, Cannon PM, Ramsdale EE, Griffiths JC, Romano G, Kingsman SM, Kingsman AJ. A transient three-plasmid expression system for the production of high titer retroviral vectors. Nucleic Acids Res. 1995;23:628–33.CrossRefPubMedPubMedCentral

32.

Hierholzer JC, Killington RA. Virus isolation and quantitation. In: Virology Methods Manual: Elsevier; 1996. p. 25–46. doi:10.1016/B978-012465330-6/50003-8.

33.

von Rhein C, Weidner T, Henß L, Martin J, Weber C, Sliva K, Schnierle BS. Curcumin and Boswellia serrata gum resin extract inhibit chikungunya and vesicular stomatitis virus infections in vitro. Antivir Res. 2016;125:51–7. doi:10.1016/j.antiviral.2015.11.007.CrossRef

34.

Weber C, Sliva K, von Rhein C, Kümmerer BM, Schnierle BS. The green tea catechin, epigallocatechin gallate inhibits chikungunya virus infection. Antivir Res. 2015;113:1–3. doi:10.1016/j.antiviral.2014.11.001.CrossRefPubMed

35.

Cureton DK, Massol RH, Saffarian S, Kirchhausen TL, Whelan, Sean P J. Vesicular stomatitis virus enters cells through vesicles incompletely coated with clathrin that depend upon actin for internalization. PLoS Pathog. 2009;5:e1000394. doi:10.1371/journal.ppat.1000394

36.

de Clercq E. Suramin in the treatment of AIDS: Mechanism of action. Antiviral Res. 1987;7:1–10. doi:10.1016/0166-3542(87)90034-9.CrossRefPubMed

37.

Schulze A, Gripon P, Urban S. Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. Hepatology. 2007;46:1759–68. doi:10.1002/hep.21896.CrossRefPubMed

38.

Eisenberger MA, Sinibaldi V, Reyno L. Suramin. Cancer Pract. 1995;3:187–9.PubMed

39.

McGeary RP, Bennett AJ, Tran QB, Cosgrove KL, Ross BP. Suramin: clinical uses and structure-activity relationships. Mini Rev Med Chem. 2008;8:1384–94.CrossRefPubMed

40.

Cooper MR, Lieberman R, La Rocca RV, Renato V, Gernt PR, Weinberger MS, Headlee DJ, et al. Adaptive control with feedback strategies for suramin dosing. Clin Pharmacol Ther. 1992;52:11–23. doi:10.1038/clpt.1992.97.CrossRefPubMed

41.

Babalola OE. Ocular onchocerciasis: current management and future prospects. Clin Ophthalmol. 2011;5:1479–91. doi:10.2147/OPTH.S8372.CrossRefPubMedPubMedCentral

42.

Stein CA, LaRocca RV, Thomas R, McAtee N, Myers CE. Suramin: an anticancer drug with a unique mechanism of action. J Clin Oncol. 1989;7:499–508.PubMed

43.

Balzarini J, Mitsuya H, de Clercq E, Broder S. Aurintricarboxylic acid and Evans Blue represent two different classes of anionic compounds which selectively inhibit the cytopathogenicity of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus. Biochem Biophys Res Commun. 1986;136:64–71.CrossRefPubMed

44.

Hawking F. Suramin: with special reference to onchocerciasis. Adv Pharmacol Chemother. 1978;15:289–322.CrossRefPubMed

45.

Weitberg AB, Mayer K, Miller ME, Mikolich DJ. Dysplastic carcinoid tumor and AIDS-related complex. N Engl J Med. 1986;314:1455. doi:10.1056/NEJM198605293142216.PubMed

46.

Horne 3rd MK, Stein CA, La Rocca RV, Myers CE. Circulating glycosaminoglycan anticoagulants associated with suramin treatment. Blood. 1988;71:273–9.PubMed

47.

Kouznetsova J, Sun W, Martínez-Romero C, Tawa G, Shinn P, Chen CZ, et al. Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs. Emerg Microbes Infect. 2014;3:e84. doi:10.1038/emi.2014.88.CrossRefPubMedPubMedCentral

48.

Gehring G, Rohrmann K, Atenchong N, Mittler E, Becker S, Dahlmann F, et al. The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry. J Antimicrob Chemother. 2014;69:2123–31. doi:10.1093/jac/dku091.CrossRefPubMed

Title: Suramin is a potent inhibitor of Chikungunya and Ebola virus cell entry
Authors: Lisa Henß
Simon Beck
Tatjana Weidner
Nadine Biedenkopf
Katja Sliva
Christopher Weber
Stephan Becker
Barbara S. Schnierle
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Virology Journal / Issue 1/2016
Electronic ISSN: 1743-422X
DOI: https://doi.org/10.1186/s12985-016-0607-2

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