Skip to main content
SpringerLink
Log in

An Industry Perspective on Dengue Drug Discovery and Development

  • Chapter
  • First Online:
Dengue and Zika: Control and Antiviral Treatment Strategies

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1062))

Abstract

Dengue is the most important mosquito-borne viral disease in the world, representing a major unmet medical need and a growing public health concern. The disease imposes a heavy burden to the affected individuals, to the health care systems, and to the economies of endemic countries. Vector control is the most widespread tool to curb dengue epidemics, but has been insufficient. Therefore, additional means such as vaccines and antivirals are required to aid in a coordinated response. The discovery and development of small molecule dengue virus inhibitors as a tool to prevent and/or treat dengue disease faces major hurdles in combining pan-serotypic efficacy, safety, and optimal drug-like properties. Moreover, the financial return of dengue drug projects may not compensate for the initial investment in research and development. This review article addresses the efforts undertaken to face the dengue epidemics, focusing on antiviral drug development. The dengue drug research and development process is described in detail and a dengue antiviral target product profile is proposed. The article discusses collaborations between the different players in the research field: government and government-sponsored organizations, pharmaceutical and biotechnology companies, academia, and non-profit and philanthropic organizations. Public-private partnerships are proposed as a model to boost dengue research and development towards an approved antiviral drug in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

DENV:

dengue virus

DVI:

Dengue Vaccine Initiative

PPP:

private public partnership

R&D:

Research and Development

SAR:

Structure Relationship Activity

WHO:

World Health Organization

References

  1. Achee NL, Fred Gould TAP, Reiner RC Jr, Morrison AC, Ritchie SA, Gubler DJ, Teyssou R, Scott TW (2015) A critical assessment of vector control for Dengue prevention. PLoS Negl Trop Dis 9(5):e0003655. https://doi.org/10.1371/journal.pntd.0003655

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Austin JE (2000) The collaboration challenge: how nonprofits and business succeed through strategic alliances. Jossey-Bass, San Francisco

    Google Scholar 

  3. Avorn J (2015) The $2.6 Billion Pill – methodologic and policy considerations. N Engl J Med 372(20):1877–1879. https://doi.org/10.1056/NEJMp1500848

    Article  PubMed  CAS  Google Scholar 

  4. Bagley CE, Tvarno CD (2013) Pharmaceutical public-private partnerships in the United States and Europe: moving from the bench to the bedside. Lecturer and Other Affiliate Scholarship Series 12 (Paper 12)

    Google Scholar 

  5. Beatty ME, Beutels P, Meltzer MI, Shepard DS, Hombach J, Hutubessy R, Dessis D et al (2011) Health economics of Dengue: a systematic literature review and expert panel’s assessment. Am J Trop Med Hyg 84(3):473–488. https://doi.org/10.4269/ajtmh.2011.10-0521

    Article  PubMed  PubMed Central  Google Scholar 

  6. Beauté J, Vong S (2010) Cost and disease burden of Dengue in Cambodia. BMC Public Health 10(1):521. https://doi.org/10.1186/1471-2458-10-521

    Article  PubMed  PubMed Central  Google Scholar 

  7. Behnam MAM, Nitsche C, Boldescu V, Klein CD (2016) The medicinal chemistry of Dengue virus. J Med Chem 59(12):5622–5649. https://doi.org/10.1021/acs.jmedchem.5b01653

    Article  PubMed  CAS  Google Scholar 

  8. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM et al (2013) The global distribution and burden of dengue. Nature 496(7446):504–507. https://doi.org/10.1038/nature12060

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Blass BE (2015) Chapter 1 – drug discovery and development: an overview of modern methods and principles. In: Blass BE (ed) Basic principles of drug discovery and development. Academic Press, Boston, pp 1–34

    Google Scholar 

  10. Blum LC, Reymond J-L (2009) 970 million druglike small molecules for virtual screening in the chemical universe database GDB-13. J Am Chem Soc 131(25):8732–8733. https://doi.org/10.1021/ja902302h

    Article  PubMed  CAS  Google Scholar 

  11. Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS, Hoen AG, Moyes CL et al (2012) Refining the global spatial limits of Dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis 6(8):e1760. https://doi.org/10.1371/journal.pntd.0001760

    Article  PubMed  PubMed Central  Google Scholar 

  12. Calisher CH, Karabatsos N, Dalrymple JM, Shope RE, Porterfield JS, Westaway EG, Brandt WE (1989) Antigenic relationships between Flaviviruses as determined by cross-neutralization tests with polyclonal antisera. J Gen Virol 70(1):37–43. https://doi.org/10.1099/0022-1317-70-1-37

    Article  PubMed  Google Scholar 

  13. Carrasco LR, Lee LK, Lee VJ, Ooi EE, Shepard DS, Thein TL, Gan V et al (2011) Economic impact of Dengue illness and the cost-effectiveness of future vaccination programs in Singapore. PLoS Negl Trop Dis 5(12):e1426. https://doi.org/10.1371/journal.pntd.0001426

    Article  PubMed  PubMed Central  Google Scholar 

  14. Carrington LB, Simmons CP (2014) Human to mosquito transmission of Dengue viruses. Front Immunol 5:290. https://doi.org/10.3389/fimmu.2014.00290

    Article  PubMed  PubMed Central  Google Scholar 

  15. Chan KWK, Watanabe S, Kavishna R, Alonso S, Vasudevan SG (2015) Animal models for studying dengue pathogenesis and therapy. Antiviral Res 123:5–14. https://doi.org/10.1016/j.antiviral.2015.08.013

    Article  PubMed  CAS  Google Scholar 

  16. Chang J, Block TM, Guo J-T (2013) Antiviral therapies targeting host ER alpha-glucosidases: current status and future directions. Antivir Res 99(3):251–260. https://doi.org/10.1016/j.antiviral.2013.06.011

    Article  PubMed  CAS  Google Scholar 

  17. Chapman N, Doubell A, Oversteegen L, Chowdhary V, Rugarabamu G, Zanetti R, Ong M, Borri J (2017) G-Finder 2017 report. Neglected disease research and development: Reflecting on a decade of global investment. Policy Cures. Accessed 12 March 2018. http://policycuresresearch.org/downloads/Y10_G-FINDER_full_report.pdf

  18. ClinicalTrials.gov (2014) Efficacy and safety of ivermectin against dengue infection. NCT02045069. Last Modified October 29, 2015. Accessed 12 Jan. https://clinicaltrials.gov/ct2/show/NCT02045069

  19. ClinicalTrials.gov (2014) Study to determine the safety, tolerability and pharmacokinetics of UV-4B solution administered orally in healthy subjects (UV). NCT02061358. Last Modified September 17, 2016. Accessed 12 Jan. https://clinicaltrials.gov/ct2/show/results/NCT02061358

  20. ClinicalTrials.gov (2015) Celgosivir or modipafant as treatment for adult participants with uncomplicated Dengue fever in Singapore. NCT02569827. Last Modified April 19, 2016. Accessed 11 Jan. https://clinicaltrials.gov/ct2/show/NCT02569827

  21. ClinicalTrials.gov (2015) Ketotifen as a Treatment for Vascular Leakage During Dengue Fever (KETODEN). NCT02673840. Last Modified Februry 3, 2016. Accessed 11 Jan. https://clinicaltrials.gov/ct2/show/record/NCT02673840

  22. Croft SL (2005) Public-private partnership: from there to here. Trans R Soc Trop Med Hyg 99(Supplement 1):S9–S14. https://doi.org/10.1016/j.trstmh.2005.06.008

    Article  PubMed  Google Scholar 

  23. Demotes-Mainard J, Canet E, Segard L (2006) Publi-private partnership models in France and Europe. Therapie 61(4):325–334

    Article  PubMed  Google Scholar 

  24. Dickson M, Gagnon JP (2004) Key factors in the rising cost of new drug discovery and development. Nat Rev Drug Discov 3(5):417–429

    Article  CAS  PubMed  Google Scholar 

  25. DiMasi JA, Grabowski HG, Hansen RW (2015) The cost of drug development. N Engl J Med 372(20):1972–1972. https://doi.org/10.1056/NEJMc1504317

    Article  PubMed  Google Scholar 

  26. Durbin AP, Vargas MJ, Wanionek K, Hammond SN, Gordon A, Rocha C, Balmaseda A, Harris E (2008) Phenotyping of peripheral blood mononuclear cells during acute dengue illness demonstrates infection and increased activation of monocytes in severe cases compared to classic dengue fever. Virology 376(2):429–435. https://doi.org/10.1016/j.virol.2008.03.028

    Article  PubMed  CAS  Google Scholar 

  27. DVI (2016) Dengue vaccine initiative. Accessed 20 Oct. 2016. http://www.denguevaccines.org/vaccine-development

  28. Dye C, Bartolomeos K, Moorthy V, Kieny MP (2016) Data sharing in public health emergencies: a call to researchers. Bull World Health Organ 94:158. https://doi.org/10.2471/BLT.16.170860

    Article  PubMed  PubMed Central  Google Scholar 

  29. Edillo FE, Halasa YA, Largo FM, Erasmo JNV, Amoin NB, Alera MTP, Yoon I-K, Alcantara AC, Shepard DS (2015) Economic cost and burden of Dengue in the Philippines. Am J Trop Med Hyg 92(2):360–366. https://doi.org/10.4269/ajtmh.14-0139

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ekins S, Mestres J, Testa B (2007) In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. Br J Pharmacol 152(1):9–20. https://doi.org/10.1038/sj.bjp.0707305

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. EUVIRNA (2015) European training network on (+)RNA virus replication and antiviral drug development. Accessed 30 Nov. http://euvirna.phrmy.cf.ac.uk/?q=node/2

  32. FDA (2008) Guidance for industry. Tropical disease priority review vouchers. Accessed 20 Jan. https://www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2008-D-0530-gdl.pdf

  33. FDA (2015) The drug development process. Last Modified 24 June 2015. Accessed 29 Nov. http://www.fda.gov/ForPatients/Approvals/Drugs/ucm405658.htm

  34. Fischl W, Bartenschlager R (2013) High-throughput screening using Dengue virus reporter genomes. In: Gong EY (ed) Antiviral methods and protocols. Humana Press, New York, pp 205–219

    Chapter  Google Scholar 

  35. Foundation-Merieux (2016) Partnership for Dengue control. Accessed 13 Dec. http://www.controldengue.org/about-us/

  36. Gaspar R, Aksu B, Cuine A, Danhof M, Takac MJ-M, Linden HH, Link A et al (2012) Towards a European strategy for medicines research (2014–2020): the EUFEPS position paper on Horizon 2020. Eur J Pharm Sci 47(5):979–987. https://doi.org/10.1016/j.ejps.2012.09.020

    Article  PubMed  CAS  Google Scholar 

  37. Gjenero-Margan I, Aleraj B, Krajcar D, Lesnikar V, Klobučar A, Pem-Novosel I, Kurečić-Filipović S, Komparak S, Martić R, Đuričić S, Betica-Radić L, Okmadžić J, Vilibić-Čavlek T, Babić Erceg A, Turković B, Avšić-Županc T, Radić I, Ljubić M, Šarac K, Benić N, Mlinarić-Galinović G (2011) Autochthonous dengue fever in Croatia, August–September 2010. Euro Surveill 16(9):19805–19808

    PubMed  Google Scholar 

  38. Gu F, Shi P-Y (2014) The challenges of dengue drug discovery and development. Clin Investig 4(8):683–685. https://doi.org/10.4155/cli.14.67

    Article  CAS  Google Scholar 

  39. Gubler DJ (2008) Dengue/Dengue haemorrhagic fever: history and current status. In: Bock G, Goode J (eds) New treatment strategies for Dengue and other Flaviviral diseases: novartis foundation symposium 277. Wiley, Chichester, pp 3–22

    Chapter  Google Scholar 

  40. Hales S, de Wet N, Maindonald J, Woodward A (2002) Potential effect of population and climate changes on global distribution of dengue fever: an empirical model. Lancet 360(9336):830–834. https://doi.org/10.1016/S0140-6736(02)09964-6

    Article  PubMed  Google Scholar 

  41. Hefti FF (2008) Requirements for a lead compound to become a clinical candidate. BMC Neurosci 9(Suppl 3):S7–S7. https://doi.org/10.1186/1471-2202-9-S3-S7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Horstick O, Tozan Y, Wilder-Smith A (2015) Reviewing Dengue: still a neglected tropical disease? PLoS Negl Trop Dis 9(4):e0003632. https://doi.org/10.1371/journal.pntd.0003632

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Hotez PJ, Alvarado M, Basáñez M-G, Bolliger I, Bourne R, Boussinesq M, Brooker SJ et al (2014) The global burden of disease study 2010: interpretation and implications for the neglected tropical diseases. PLoS Negl Trop Dis 8(7):e2865. https://doi.org/10.1371/journal.pntd.0002865

    Article  PubMed  PubMed Central  Google Scholar 

  44. Hughes JP, Rees S, Kalindjian SB, Philpott KL (2011) Principles of early drug discovery. Br J Pharmacol 162(6):1239–1249. https://doi.org/10.1111/j.1476-5381.2010.01127.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Ian HG, Didier L, Frearson Julie A (2011) Finding new hits in neglected disease projects: target or phenotypic based screening? Curr Top Med Chem 11(10):1284–1291. https://doi.org/10.2174/156802611795429176

    Article  Google Scholar 

  46. Jomo KS, Chowdhury A, Sharma K, Platz D (2016) Public-private partnerships and the 2030 Agenda for sustainable development: fit for purpose?: United Nations, Department of Economics and Social Affairs

    Google Scholar 

  47. Kaptein SJF, Neyts J (2016) Towards antiviral therapies for treating dengue virus infections. Curr Opin Pharmacol 30:1–7. https://doi.org/10.1016/j.coph.2016.06.002

    Article  PubMed  CAS  Google Scholar 

  48. Katsuno K, Burrows JN, Duncan K, van Huijsduijnen RH, Kaneko T, Kita K, Mowbray CE et al (2015) Hit and lead criteria in drug discovery for infectious diseases of the developing world. Nat Rev Drug Discov 14(11):751–758. https://doi.org/10.1038/nrd4683

    Article  PubMed  CAS  Google Scholar 

  49. Katzelnick LC, Fonville JM, Gromowski GD, Arriaga JB, Green A, James SL, Lau L et al (2015) Dengue viruses cluster antigenically but not as discrete serotypes. Science 349(6254):1338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Khormi HM, Kumar L (2011) Modeling dengue fever risk based on socioeconomic parameters, nationality and age groups: GIS and remote sensing based case study. Sci Total Environ 409(22):4713–4719. https://doi.org/10.1016/j.scitotenv.2011.08.028

    Article  PubMed  CAS  Google Scholar 

  51. Kieny M-P, Moorthy V, Bagozzi D (2016) Public health: use open data to curb Zika virus. Nature 533(7604):469–469. https://doi.org/10.1038/533469b

    Article  PubMed  CAS  Google Scholar 

  52. Krishnan MN, Garcia-Blanco MA (2014) Targeting host factors to treat West Nile and Dengue viral infections. Virus 6(2):683–708. https://doi.org/10.3390/v6020683

    Article  CAS  Google Scholar 

  53. KULeuven-News (2013) Wellcome trust, KU Leuven and Janssen join forces to combat dengue fever. Accessed 20 Oct. https://www.kuleuven.be/english/news/2013/wellcome-trust-ku-leuven-and-janssen-join-forces-to-combat-dengue-fever

  54. Leeson P (2012) Drug discovery: chemical beauty contest. Nature 481(7382):455–456

    Article  CAS  PubMed  Google Scholar 

  55. Lim SP, Wang Q-Y, Noble CG, Chen Y-L, Dong H, Zou B, Yokokawa F et al (2013) Ten years of dengue drug discovery: progress and prospects. Antivir Res 100(2):500–519. https://doi.org/10.1016/j.antiviral.2013.09.013

    Article  PubMed  CAS  Google Scholar 

  56. Lourenço J, Recker M (2014) The 2012 Madeira Dengue outbreak: epidemiological determinants and future epidemic potential. PLoS Negl Trop Dis 8(8):e3083. https://doi.org/10.1371/journal.pntd.0003083

    Article  PubMed  PubMed Central  Google Scholar 

  57. Low JG, Sung C, Wijaya L, Wei Y, Rathore APS, Watanabe S, Tan BH et al (2014) Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet Infect Dis 14(8):706–715. https://doi.org/10.1016/S1473-3099(14)70730-3

    Article  PubMed  CAS  Google Scholar 

  58. Magariños MP, Carmona SJ, Crowther GJ, Ralph SA, Roos DS, Shanmugam D, Van Voorhis WC, Agüero F (2012) TDR targets: a chemogenomics resource for neglected diseases. Nucleic Acids Res 40(Database issue):D1118–D1127. https://doi.org/10.1093/nar/gkr1053

    Article  PubMed  CAS  Google Scholar 

  59. Martina BEE, Koraka P, Osterhaus ADME (2009) Dengue virus pathogenesis: an integrated view. Clin Microbiol Rev 22(4):564–581. https://doi.org/10.1128/cmr.00035-09

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Medeiros LC d C, Castilho CAR, Braga C, de Souza WV, Regis L, Monteiro AMV (2011) Modeling the dynamic transmission of Dengue fever: investigating disease persistence. PLoS Negl Trop Dis 5(1):e942. https://doi.org/10.1371/journal.pntd.0000942

    Article  PubMed Central  Google Scholar 

  61. Messina JP, Brady OJ, Scott TW, Zou C, Pigott DM, Duda KA, Bhatt S et al (2013) Global spread of dengue virus types: mapping the 70 year history. Trends Microbiol 22(3):138–146. https://doi.org/10.1016/j.tim.2013.12.011

    Article  CAS  Google Scholar 

  62. Moi, ML, Takasaki T, Kurane I (2016) Human antibody response to dengue virus: implications for dengue vaccine design. Trop Med Health 44(1) https://doi.org/10.1186/s41182-016-0004-y

  63. Moran M, Chapman N, Abela-Oversteegen L, Chowdhary V, Doubell A, Whittall C, Howard R et al (2015). G-FInder 2015 report. Neglected disease research and development: the Ebola effect. Policy cures. Accessed 23 Nov 2016. http://policycures.org/downloads/Y8GFINDER full report web.pdf

  64. NIH (2016) National institute of allergy and infectious diseases. Dengue fever. NIH. Accessed 30 Nov. https://www.niaid.nih.gov/diseases-conditions/dengue-fever

  65. Noble CG, Chen Y-L, Dong H, Feng G, Lim SP, Schul W, Wang Q-Y, Shi P-Y (2010) Strategies for development of dengue virus inhibitors. Antivir Res 85(3):450–462. https://doi.org/10.1016/j.antiviral.2009.12.011

    Article  PubMed  CAS  Google Scholar 

  66. Noble CG, Shi P-Y (2013) Difficulties and advancements in developing drugs for the treatment of dengue fever. Expert Opin Orphan Drugs 1(12):947–949. https://doi.org/10.1517/21678707.2013.858597

    Article  CAS  Google Scholar 

  67. Nwaka S, Hudson A (2006) Innovative lead discovery strategies for tropical diseases. Nat Rev Drug Discov 5(11):941–955

    Article  CAS  PubMed  Google Scholar 

  68. Nwaka S, Ridley RG (2003) Virtual drug discovery and development for neglected diseases through public-private partnerships. Nat Rev Drug Discov 2(11):919–928

    Article  CAS  PubMed  Google Scholar 

  69. Ong A, Sandar M, Chen MI, Sin LY (2007) Fatal dengue hemorrhagic fever in adults during a dengue epidemic in Singapore. Int J Infect Dis 11(3):263–267. https://doi.org/10.1016/j.ijid.2006.02.012

    Article  PubMed  Google Scholar 

  70. Owens J (2007) Determining druggability. Nat Rev Drug Discov 6(3):187–187

    Article  CAS  Google Scholar 

  71. Pang EL, Loh H-S (2017) Towards development of a universal dengue vaccine – how close are we? Asian Pac J Trop Med 10(3):220–228. https://doi.org/10.1016/j.apjtm.2017.03.003

    Article  PubMed  CAS  Google Scholar 

  72. Paul SM, Mytelka DS, Dunwiddie CT, Persinger CC, Munos BH, Lindborg SR, Schacht AL (2010) How to improve R&D productivity: the pharmaceutical industry’s grand challenge. Nat Rev Drug Discov 9(3):203–214. http://www.nature.com/nrd/journal/v9/n3/suppinfo/nrd3078_S1.html

    Article  CAS  PubMed  Google Scholar 

  73. Perry ST, Buck MD, Plummer EM, Penmasta RA, Batra H, Stavale EJ, Warfield KL et al (2013) An iminosugar with potent inhibition of dengue virus infection in vivo. Antivir Res 98(1):35–43. https://doi.org/10.1016/j.antiviral.2013.01.004

    Article  PubMed  CAS  Google Scholar 

  74. PPPIRC (2016) Public-private-partnership in infrastructure resource center. Government objectives: benefits and risks of PPPs. World Bank Group, Last Modified 31 October 2016. Accessed 13 Dec. https://ppp.worldbank.org/public-private-partnership/overview/ppp-objectives

  75. Runge-Ranzinger S, Kroeger A, Olliaro P, McCall PJ, Tejeda GS, Lloyd LS, Hakim L et al (2016) Dengue contingency planning: from research to policy and practice. PLoS Negl Trop Dis 10(9):e0004916. https://doi.org/10.1371/journal.pntd.0004916

    Article  PubMed  PubMed Central  Google Scholar 

  76. SAGE (2016) Summary of the April 2016 meeting of the Strategic Advisory Group of Experts on Immunization (SAGE) – Dengue Vaccine. Accessed 11 Oct. http://www.who.int/immunization/sage/meetings/2016/april/SAGE_April_2016_Meeting_Web_summary.pdf?ua=1

  77. Sampath A, Padmanabhan R (2009) Molecular targets for flavivirus drug discovery. Antivir Res 81(1):6–15. https://doi.org/10.1016/j.antiviral.2008.08.004

    Article  PubMed  CAS  Google Scholar 

  78. Souza S, Fernando H, da Silva Almeida B, Boscardin SB (2016) Early dengue virus interactions: the role of dendritic cells during infection. Virus Res 223:88–98. https://doi.org/10.1016/j.virusres.2016.07.001

    Article  CAS  Google Scholar 

  79. Satoshi K, Yasuyuki K, Ling MM, Akira K, Masayuki O, Koh S, Tetsuro K et al (2015) Autochthonous Dengue fever, Tokyo, Japan, 2014. Emer Infect Dis J 21(3):517. https://doi.org/10.3201/eid2103.141662

    Article  CAS  Google Scholar 

  80. Scannell JW, Blanckley A, Boldon H, Warrington B (2012) Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov 11(3):191–200. http://www.nature.com/nrd/journal/v11/n3/suppinfo/nrd3681_S1.html

    Article  CAS  PubMed  Google Scholar 

  81. Scherwitzl I, Mongkolsapaja J, Screaton G (2017) Recent advances in human flavivirus vaccines. Curr Opin Virol 23:95–101. https://doi.org/10.1016/j.coviro.2017.04.002

    Article  PubMed  CAS  Google Scholar 

  82. Schmid MA, Diamond MS, Harris E (2014) Dendritic cells in Dengue virus infection: targets of virus replication and mediators of immunity. Front Immunol 5:647. https://doi.org/10.3389/fimmu.2014.00647

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Schuhmacher A, Gassmann O, Hinder M (2016) Changing R&D models in research-based pharmaceutical companies. J Transl Med 14:105. https://doi.org/10.1186/s12967-016-0838-4

    Article  PubMed  PubMed Central  Google Scholar 

  84. Shepard DS, Coudeville L, Halasa YA, Zambrano B, Dayan GH (2011) Economic impact of dengue illness in the Americas. Am J Trop Med Hyg 84(2):200–207. https://doi.org/10.4269/ajtmh.2011.10-0503

    Article  PubMed  PubMed Central  Google Scholar 

  85. Shepard DS, Halasa YA, Tyagi BK, Vivek Adhish S, Nandan D, Karthiga KS, Chellaswamy V et al (2014) Economic and disease burden of Dengue illness in India. Am J Trop Med Hyg 91(6):1235–1242. https://doi.org/10.4269/ajtmh.14-0002

    Article  PubMed  PubMed Central  Google Scholar 

  86. Shepard DS, Undurraga EA, Halasa YA (2013) Economic and disease burden of Dengue in Southeast Asia. PLoS Negl Trop Dis 7(2):e2055. https://doi.org/10.1371/journal.pntd.0002055

    Article  PubMed  PubMed Central  Google Scholar 

  87. Shepard DS, Undurraga EA, Halasa YA, Stanaway JD (2016) The global economic burden of dengue: a systematic analysis. Lancet Infect Dis 16(8):935–941. https://doi.org/10.1016/S1473-3099(16)00146-8

    Article  PubMed  Google Scholar 

  88. Souza DG, Fagundes CT, Sousa LP, Amaral FA, Souza RS, Souza AL, Kroon EG et al (2009) Essential role of platelet-activating factor receptor in the pathogenesis of Dengue virus infection. Proc Natl Acad Sci 106(33):14138–14143. https://doi.org/10.1073/pnas.0906467106

    Article  PubMed  PubMed Central  Google Scholar 

  89. St. John AL, Abraham SN, Gubler DJ (2013) Barriers to preclinical investigations of anti-dengue immunity and dengue pathogenesis. Nat Rev Microbiol 11(6):420–426. https://doi.org/10.1038/nrmicro3030

    Article  PubMed  CAS  Google Scholar 

  90. Succo T, Leparc-Goffart I, Ferré J, Roiz D, Broche B, Maquart M, Noel H, Catelinois O, Entezam F, Caire D, Jourdain F, Esteve-Moussion I, Cochet A, Paupy C, Rousseau C, Paty M, Golliot F (2015) Autochthonous dengue outbreak in Nîmes, South of France, July to September 2015. Euro Surveill 21(21):30240. https://doi.org/10.2807/1560-7917.ES.2016.21.21.30240

    Article  Google Scholar 

  91. Teets FD, Ramgopal MN, Sweeney KD, Graham AS, Michael SF, Isern S (2014) Origin of the dengue virus outbreak in Martin County, Florida, USA 2013. Virol Rep 1-2:2–8. https://doi.org/10.1016/j.virep.2014.05.001

    Article  PubMed  PubMed Central  Google Scholar 

  92. Trouiller P, Olliaro P, Torreele E, Orbinski J, Laing R, Ford N (2002) Drug development for neglected diseases: a deficient market and a public-health policy failure. Lancet 359(9324):2188–2194. https://doi.org/10.1016/S0140-6736(02)09096-7

    Article  PubMed  Google Scholar 

  93. UNITEDengue (2012) UNited in tackling epidemic Dengue. Accessed 15 Sept. https://www.unitedengue.org/

  94. Van Voorhis WC, Adams JH, Adelfio R, Ahyong V, Akabas MH, Alano P, Alday A et al (2016) Open source drug discovery with the Malaria box compound collection for neglected diseases and beyond. PLoS Pathog 12(7):e1005763. https://doi.org/10.1371/journal.ppat.1005763

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Warfield KL, Plummer EM, Sayce AC, Alonzi DS, Tang W, Tyrrell BE, Hill ML et al (2016) Inhibition of endoplasmic reticulum glucosidases is required for in vitro and in vivo dengue antiviral activity by the iminosugar UV-4. Antivir Res 129:93–98. https://doi.org/10.1016/j.antiviral.2016.03.001

    Article  PubMed  CAS  Google Scholar 

  96. Wellcome-Trust (2016) Sharing data during Zika nd other global health emergencies. Last Modified 10 February 2016. Accessed 14 Dec. https://blog.wellcome.ac.uk/2016/02/10/sharing-data-during-zika-and-other-global-health-emergencies/

  97. Wells TNC, Willis P, Burrows JN, van Huijsduijnen RH (2016) Open data in drug discovery and development: lessons from malaria. Nat Rev Drug Discov 15(10):661–662. https://doi.org/10.1038/nrd.2016.154

    Article  PubMed  CAS  Google Scholar 

  98. Whitehorn J, Van Vinh Nguyen C, Khanh LP, Kien DTH, Quyen NTH, Tran NTT, Hang NT et al (2016) Lovastatin for the treatment of adult patients with Dengue: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis 62(4):468–476. https://doi.org/10.1093/cid/civ949

    Article  PubMed  CAS  Google Scholar 

  99. Whitehorn J, Van VCN, Simmons CP (2014) Dengue human infection models supporting drug development. J Infect Dis 209(Suppl 2):S66–S70. https://doi.org/10.1093/infdis/jiu062

    Article  PubMed  PubMed Central  Google Scholar 

  100. Whitehorn J, Yacoub S, Anders KL, Macareo LR, Cristina Cassetti M, Van VCN, Shi P-Y, Wills B, Simmons CP (2014) Dengue therapeutics, chemoprophylaxis, and allied tools: state of the art and future directions. PLoS Negl Trop Dis 8(8):e3025. https://doi.org/10.1371/journal.pntd.0003025

    Article  PubMed  PubMed Central  Google Scholar 

  101. Whitehorn J, Simmons CP (2011) The pathogenesis of dengue. Vaccine 29(42):7221–7228. https://doi.org/10.1016/j.vaccine.2011.07.022

    Article  PubMed  CAS  Google Scholar 

  102. WHO (2007) Regional office for South-East Asia. Core group for Asia-Pacific dengue partnership: report of the meeting, Singapore, 8–10 February 2007. Accessed 14 Dec. http://www.who.int/iris/handle/10665/204914

  103. WHO (2009) Dengue guidelines for diagnosis, treatment, prevention and control. New ed. Geneva, Switzerland World Health Organization and the Special Programme for Research and Training in Tropical Diseases. electronic

    Google Scholar 

  104. WHO (2012) Global strategy for dengue prevention and control, 2012–2020. [WHO report]. Accessed 30 Sept. http://apps.who.int/iris/bitstream/10665/75303/1/9789241504034_eng.pdf?ua=1

  105. WHO (2014) Dengue and severe dengue. Fact sheet. Last Modified July 2016. Accessed 22 Nov. http://www.who.int/mediacentre/factsheets/fs117/en/

  106. WHO (2016) Dengue vaccine: WHO position paper – July 2016. Wkly Epidemiol Rec 91(30):349–364

    Google Scholar 

  107. Widdus R (2001) Public-private partnerships for health: their main targets, their diversity, and their future directions. Bull World Health Org 79:713–720

    PubMed  PubMed Central  CAS  Google Scholar 

  108. Widdus R (2005) Public-private partnerships: an overview. Trans R Soc Trop Med Hyg 99(Supplement 1):S1–S8. https://doi.org/10.1016/j.trstmh.2005.06.005

    Article  PubMed  Google Scholar 

  109. Wishart DS, Knox C, An CG, Shrivastava S, Hassanali M, Stothard P, Chang Z, Woolsey J (2006) DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res 34(suppl 1):D668–D672. https://doi.org/10.1093/nar/gkj067

    Article  CAS  PubMed  Google Scholar 

  110. Xie X, Zou J, Wang Q-Y, Shi P-Y (2015) Targeting dengue virus NS4B protein for drug discovery. Antivir Res 118(0):39–45. https://doi.org/10.1016/j.antiviral.2015.03.007

    Article  PubMed  CAS  Google Scholar 

  111. Zheng W, Thorne N, McKew JC (2013) Phenotypic screens as a renewed approach for drug discovery. Drug Discov Today 18(0):1067–1073. https://doi.org/10.1016/j.drudis.2013.07.001

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Zmurko J, Neyts J, Dallmeier K (2015) Flaviviral NS4b, chameleon and jack-in-the-box roles in viral replication and pathogenesis, and a molecular target for antiviral intervention. Rev Med Virol 25(4):205–223. https://doi.org/10.1002/rmv.1835

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Zou G, Hao Ying X, Qing M, Wang Q-Y, Shi P-Y (2011) Development and characterization of a stable luciferase dengue virus for high-throughput screening. Antivir Res 91(1):11–19. https://doi.org/10.1016/j.antiviral.2011.05.001

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Janssen Pharmaceutica NV, Janssen Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium

    Ilane Hernandez-Morales

  2. Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, University of Leuven (KU Leuven), Leuven, Belgium

    Ilane Hernandez-Morales

  3. Janssen Research & Development, Janssen Pharmaceutica NV, Janssen Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium

    Marnix Van Loock

Authors
  1. Ilane Hernandez-Morales
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marnix Van Loock
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Biochemistry, University of Lübeck, Lübeck, Germany

    Rolf Hilgenfeld

  2. Emerging Infectious Diseases Program, Duke-NUS Medical School Singapore, Singapore, Singapore

    Subhash G. Vasudevan

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hernandez-Morales, I., Van Loock, M. (2018). An Industry Perspective on Dengue Drug Discovery and Development. In: Hilgenfeld, R., Vasudevan, S. (eds) Dengue and Zika: Control and Antiviral Treatment Strategies. Advances in Experimental Medicine and Biology, vol 1062. Springer, Singapore. https://doi.org/10.1007/978-981-10-8727-1_23

Download citation

Publish with us

Policies and ethics

Search

Navigation