4.4 Review

Pengue virus RNA polymerase NS5: A potential therapeutio target?

Journal

CURRENT DRUG TARGETS
Volume 7, Issue 12, Pages 1623-1638

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138945006779025383

Keywords

dengue; NS5; nuclear targeting; nuclear protein import; RNA dependent-RNA polymerase; antivirals; therapeutics

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Dengue fever (DF)/dengue haemorrhagic fever (DHF) is the most common arthropod-borne viral infection, where it is now estimated that 2.5-3 billion people world-wide are at risk of infection. Currently there is no available treatments in the form of vaccine or drug, making eradication of the mosquito vector the only viable control measure, which has proved costly and of limited success. There are a number of different vaccines undergoing testing, but whilst a dengue vaccine is clearly desirable, there are several issues which make live-attenuated vaccines problematic. These include the phenomenon of anti body-dependent enhancement (ADE) and the possibility of recombination of attenuated vaccine strains with wild-type flavivirus members reverting vaccines to a virulent form. Until we gain a better. understanding of theses issues and their associated risks, the safety of any live dengue vaccine cannot be assured. It therefore may be safer and more feasible for therapeutic-based approaches to be developed as an alternative to live vaccines. As our understanding of dengue molecular biology expands, new potential targets for drugs are emerging. One of the most promising is the dengue non-structural protein 5 (NS5), the largest and most highly conserved of the dengue proteins. This review examines the unique properties of NS5, including its functions, interactions, subcellular localisation and regulation, and looks at ways in which some of these may be exploited in our quest for effective drugs.

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