In silico structure-based design of allosteric inhibitors targeting the Dengue virus NS3 helicase

ADLER, NATALIA S; FIDALGO, D.; AMREIN, F.; KAUFMAN, S; ARRAR, M.; BOLLINI, M.; CAVASOTTO, CLAUDIO N

Medellín

Workshop; Latin American Workshop in Structural Bioinformatics of Proteins; 2019

Dengue virus NS3 is a multifunctional enzyme involved in viral replication, host-immune evasion, and processing of the polyprotein precursor. The N-terminal region is classified asa serine protease and the C-terminal region is an RNA helicase (NS3Hel). It has been established that mutations in NS3Hel leading to the absence of helicase activity correlateddirectly with lack of virus replication. Therefore, NS3Hel is an attractive target for the development of antiviral agents. Helicases are nevertheless challenging drug targets becausepotent inhibitors are often not specific, so we are focused in identifying molecules that could act as allosteric inhibitors.