Infectious Disorders - Drug Targets

(Formerly Current Drug Targets - Infectious Disorders)

Jean-Marc Sabatier  
Laboratoire ERT 62 'Ingénierie des peptides à visée thérapeutique' 
Université de la Méditerranée
Faculté de Médecine Nord
Boulevard Pierre Dramard
13916 - MARSEILLE, Cedex 20
France

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New Approaches to Structure-Based Discovery of Dengue Protease Inhibitors

Author(s): S. M. Tomlinson, R. D. Malmstrom and S. J. Watowich

Affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0647.

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.

Keywords: Dengue virus (DENV), family Flaviviridae, Dengue Protease Inhibitors, DENV vaccines, malaria, Mosquitoes

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Article Details

VOLUME: 9
ISSUE: 3
Page: [327 - 343]
Pages: 17
DOI: 10.2174/1871526510909030327