We have established the existence of multiple, distinct inhibitory peptides targeting the DENV E glycoprotein and confirmed the utility of rational design using structural data for developing DENV E protein inhibitors. Applications of this strategy should also be possible for the generation and refinement of lead compounds for other viral envelope fusion proteins. It would be optimistic to propose that any single antiviral would provide an effective treatment for DENV given the enormous genetic variability of the four serotypes and multiple substrains. Different classes of inhibitors targeting the E protein and other DENV targets [44, 45] , could form the basis for the development of a combination treatment plan to combat this disease.