Office: B408 Microbiology
Office Phone: 970-491-6330
A major focus of my laboratory is studying the biochemistry of flavivirus NS5 RNA capping enzyme. The capping enzyme is a multifunctional protein that forms the mature viral RNA cap that directs viral polyprotein translation and protects the viral genome from degradation.
We recently identified that the N-terminus of the NS5 protein possesses guanylyltransferase activity in addition to the previously known methyltransferase activity. The guanylyltransferase transfers GMP from GTP to the 5' end of the viral genomic RNA, forming the 5' RNA cap structure. The flavivirus guanylyltransferase enzyme is structurally dissimilar to other known guanylyltransferase enzymes, and we are performing structure-function studies to determine how this enzyme functions. The capping enzyme binds GTP in a unique fashion, and we previously characterized the structural interactions that occur in the GTP binding site. Based on these studies, we are using a combination of high-throughput drug screening and structure-based rational drug design methodologies to develop new antiviral drugs specifically targeting the viral capping enzyme.
We also have projects focused on:
- developing transgenic mosquitoes that glow in the presence of various alphaviruses that will aid in virus transmission studies.
- development of a novel HTS screening assay to identify inhibitors of alphavirus capsid assembly.
- exploring the utility of Sindbis virus in the treatment of companion animal cancers and downregulation of chemoresistance gene function.
- developing RNA aptamers that interfere with flavivirus replication in infected cells.