Insights into Cleavage Specificity from the Crystal Structure of Foot-and-Mouth Disease Virus 3C Protease Complexed with a Peptide Substrate

Foot-and-mouth disease (FMD) is a serious, widespread viral disease of cloven-hoofed animals, including important agricultural species such as cattle, sheep, pigs and goats (19, 45). The virus spreads rapidly and, although endemic and epidemic situations can be controlled using vaccines that are based on inactivated virus particles, political and technical difficulties with the maintenance and use of vaccine stocks has stimulated the search for alternative means of tackling the disease, such as anti-viral drugs (16). The development of such treatments will demand a detailed knowledge of the molecular basis of viral replication. In this paper we focus on the structural basis of the cleavage activity of FMDV 3Cpro; as a highly conserved viral enzyme (11), FMDV 3Cpro is a potential drug target.