REPLICATION COMPLEXES OF RHDV RNA-DEPENDENT RNA POLYMERASE

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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. Rabbit Hemorrhagic disease virus (RHDV) belongs to the Caliciviridae, a family of positive-sense, single-stranded RNA viruses causing serious diseases in mammals, including humans. The viral RNA-dependent RNA polymerase (RdRP) is essential for replicating the viral genome. Hence, understanding the structural and enzymological properties of this enzyme opens avenues for developing antiviral therapeutic agents that interfere with viral replication. Previous work at SSRL has allowed us to solve structures of RHDV RdRP in a number of different conformational states, in complex with different metal ions and in complex with different nucleotides. Preliminary attempts to crystallize and solve structures of complexes with nucleic acid substrates and protein cofactors have led to the identification of a number of new crystal forms. Ongoing biochemical studies, crystallization trials and crystallographic studies are now being carried out to allow for the determination of high-resolution structures of replication complexes of RHDV RdRP.