Inhibitors of the Flavivirus Capping Enzyme
Technology ID: 11-010
Despite serious causing serious morbidity and mortality worldwide, there are no approved antiviral chemotherapeutics available for human use. The Geiss laboratory at Colorado State University together with the Keenan laboratory at University of Northern Colorado has elucidated a novel broad-spectrum anti-flaviviral target, created a high throughput screening protocol, and identified a series of small molecule lead inhibitory candidates.
These inhibitory compounds, as described in a recent Journal of Virology publication, target the enzyme that is responsible for capping the RNA viral genome. The compounds have undergone a preliminary SAR analysis that suggests additional modifications can affect affinity. In vitro the compounds demonstrate good specificity and low toxicity. Initial studies show that inhibitors of the RNA capping enzyme act on multiple flaviviruses including dengue, West Nile, and yellow fever.
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Feature and Benefits:
- Lead compound demonstrates improved activity over Ribavirin.
- GTP displacement assay allows for high throughput screening of small molecule compounds.
- The RNA capping enzyme is conserved across multiple flaviviruses including dengue, West Nile, and yellow fever viruses.
Inventors:
- Brian Geiss
- Susan Keenan
- Hilary Stahla-Beek
Related Publications:
- J. Virol. 2012 Jun 6. [Epub ahead of print]
- J Biomol Screen. 2011 Sep; (8):852-61
- J Mol Biol. 2009 Feb 6;385 (5):1643-54
Patent Information: Provisional Patent Application
