New approaches to structure-based discovery of Dengue protease inhibitors

S. M. Tomlinson, R. D. Malmstrom, S. J. Watowich

Research output: Contribution to journalReview article

48 Scopus citations

Abstract

Dengue virus (DENV), a member of the family Flaviviridae, presents a tremendous threat to global health since an estimated 2.5 billion people worldwide are at risk for epidemic transmission. DENV infections are primarily restricted to sub-tropical and tropical regions; however, there is concern that the virus will spread into new regions including the United States [1]. There are no approved antiviral drugs or vaccines to combat dengue infection, although DENV vaccines have entered Phase 3 clinical trials. Drug discovery and development efforts against DENV and other viral pathogens must overcome specificity, efficacy, safety, and resistance challenges before the shortage of licensed drugs to treat viral infections can be relieved. Current drug discovery methods are largely inefficient and thus relatively ineffective at tackling the growing threat to public health presented by emerging and remerging viral pathogens. This review discusses current and newly implemented structure-based computational efforts to discover antivirals that target the DENV NS3 protease, although it is clear that these computational tools can be applied to most disease targets.

Original languageEnglish (US)
Pages (from-to)327-343
Number of pages17
JournalInfectious Disorders - Drug Targets
Volume9
Issue number3
DOIs
StatePublished - Jun 2009

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Microbiology (medical)

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