STRUCTURE-BASED DEVELOPMENT OF INHIBITORS OF VIRAL CHYMOTRYPSIN-LIKE PROTEASES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The viral chymotrypsin-like proteases of positive-sense, single-stranded RNA viruses are an ideal target for the design of antiviral drugs. The enzymes have a unique mechanism and most have a cleavage specificity that is different from that of all known mammalian proteases. The viral proteases are also absolutely required for viral replication. Many important pathogens of humans and animals belong to this group of viruses. We and others have determined crystal structures of a number of viral chymotrypsin-like proteases, including some with bound inhibitors. This work is valuable for the understanding of viral evolution, enzymatic mechanisms and the development of anti viral drugs. We are pursuing a project to develop different and more effective inhibitors of several different viral proteases.