Design and synthesis of inhibitors of foot-and-mouth disease virus 3C protease

摘要

Foot-and-mouth disease virus (FMDV) causes a highly infectious disease of cloven-hoofed livestock with economically devastating consequences. The political and technical problems associated with the use of FMDV vaccines make drug-based disease control an attractive alternative. The FMDV genome is translated as a single polypeptide precursor that is cleaved into functional proteins by virally-encoded proteases. Ten of the thirteen cleavages are performed by the highly conserved 3C protease (3Cpro), making this enzyme an obvious target for anti-viral drugs.udThis thesis details an attempt to develop 3C protease inhibitor with efficacy against FMDV. This includes both rational drug design based on the peptide substrate of the protease, and also the high throughput screening of small molecules.