Disclosed herein is the discovery of novel NS3/4A compositions with enhanced expression abilities. Embodiments of the invention include codon optimized NS3/4A compositions and compositions with the Semliki forest virus replicon. Additional embodiments include transgenic organisms containing these NS3/4A compositions, methods or using these transgenic mice to screen and refine drugs, and the drugs refined by these methods. Additional embodiments include protease activity dependent molecules that can indicate the presence or absence of a protease inhibitor.