Currently there are few treatment options for Valley Fever.  Concerns about current antifungals include toxicity and fungistatic limitations.  Drug discovery pipelines for Valley Fever are scant, as cost vs return to discover and deliver new treatments are deterrents.  At TGen North, in collaboration with Mayo Clinic, a low cost, high throughput, primary screening assay has been developed for the discovery of new compounds efficacious against Coccidioides in a BSL2 setting, using the avirulent strain Coccidioides posadasii ?cts2/?ard1/?cts3. The method is a high-throughput 96-well culture array, and uses spectrophotometry to determine whether there are effects of the small molecule library against the growth of this strain.Mayo Clinic researchers designed a pilot Coccidioides small molecule library evaluated for activity in the assays established by the TGen team under the BSL2 conditions. This test library (~ 1800 compounds) includes 1200 approved drugs (Prestwick Chemical Library). An additional ~600 compounds were selected from the Mayo Clinic Collection (MCC) using a knowledge-driven approach, capitalizing on the Coccidioides structural data available in the Protein Data Bank. Virtual screening workflows utilizing a blend of 2D scaffold-based and 3D structure-based techniques were used to interrogate the MCC and identify compounds of potential interest for primary screening in the Coccidioides assay workflow established by the TGen team.This method is a first step towards a workable BSL3 protocol allowing screening of virulent Coccidioides immitis and posadasii. The ability to screen thousands of molecules relatively quickly and inexpensively may result in more options for effective Valley Fever treatments.

High-throughput screening for small molecules with efficacy against <i>Coccidioides</i> infection

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

High-throughput screening for small molecules with efficacy against Coccidioides infection