Towards the design of dengue virus antiviral inhibitors.

Abstract

New treatments are urgently needed to combat the increasing number of dengue fever cases in endemic countries as well as amongst a large number of travellers from nonendemic countries. The main goal of this project was to provide three-dimensional structural information to assist the design of inhibitors against dengue virus, a very important health problem with ever increasing impact including in Singapore. This goal has been attained since, using crystallographic analysis, we succeeded in solving the first structure of the NS5 polymerase domain from dengue serotype 3 (Yap et al., 2007), a much awaited structure that had been the subject of intense competition including by several American groups. Another milestone was the first structure of the NS3 helicase in complex with RNA that was published in EMBO Journal in Dec 2008 (Luo et al., 2008). Armed with these data the work can now proceed to perform structure-based drug discovery.