NS3 Helicases as Drug Targets

Members of the viral family Flaviviridae are a major cause of infectious diseases, such as hepatitis C, Dengue fever, Japanese encephalitis, Yellow fever or West Nile fever. Major efforts are therefore being made to identify medicines that can fight these infections. The genome of the Flaviviridae contains a single ORF that is translated into a precursor polyprotein which is processed in the host into several proteins. Amongst these, the nonstructural protein 3 (NS3) is formed from two domains that show distinct catalytic activities: a serine protease and a helicase activity. Since both activities are required for viral replication, there is a lot of interest in investigating NS3 as a potential drug target. On the basis of the structural information available, we shall assess here the druggability of the helicase domain of NS3. Keywords: NS3 helicase, hepatitis C virus, dengue virus, west nile virus