Strategies for development of dengue virus inhibitors

Christian G. Noble, Yen Liang Chen, Hongping Dong, Feng Gu, Siew Pheng Lim, Wouter Schul, Qing Yin Wang, Pei Yong Shi

Research output: Contribution to journalReview article

190 Scopus citations

Abstract

Antiviral drug discovery is becoming increasingly important due to the global threat of viral disease pandemics. Many members of the genus Flavivirus are significant human pathogens, among which dengue virus (DENV) alone poses a public health threat to 2.5 billion worldwide, leading to 50-100 million human infections each year. Neither vaccine nor effective therapeutics is currently available for DENV. Development of a DENV vaccine has been challenging, because of the need to simultaneously immunize and induce a long-lasting protection against all four serotypes of DENV; an incompletely immunized individual may be sensitized to life-threatening dengue hemorrhagic fever or dengue shock syndrome. The challenges associated with vaccine development have underscored the importance of development of antiviral therapies for DENV and other flaviviruses. Here we review the strategies to identify inhibitors for DENV therapy. Both viral and host proteins essential for viral replication cycle are potential targets for antiviral development. Inhibitors could be identified by multiple approaches, including enzyme-based screening, viral replication-based screening, structure-based rational design, virtual screening, and fragment-based screening. The strategies discussed in this report should be applicable to antiviral development of other viruses.

Original languageEnglish (US)
Pages (from-to)450-462
Number of pages13
JournalAntiviral research
Volume85
Issue number3
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

Keywords

  • Antiviral
  • Cell-based assay
  • Dengue virus
  • Drug discovery
  • Enzyme assay
  • Flavivirus
  • High-throughput screening

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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  • Cite this

    Noble, C. G., Chen, Y. L., Dong, H., Gu, F., Lim, S. P., Schul, W., Wang, Q. Y., & Shi, P. Y. (2010). Strategies for development of dengue virus inhibitors. Antiviral research, 85(3), 450-462. https://doi.org/10.1016/j.antiviral.2009.12.011