Abstract. One of the objectives of the National Institutes of Allergy and Infectious Diseases (NIAID) Biodefense Program is to identify or develop broad-spectrum antimicrobials for use against bioterrorism pathogens and emerging infectious agents. As a part of that program, our institution has screened the 10 000-compound MyriaScreen Diversity Collection of high-purity druglike compounds against three NIAID category A and one category B priority pathogens in an effort to identify potential compound classes for further drug development. The effective use of a Clinical and Laboratory Standards Institutebased high-throughput screening (HTS) 96-wellbased format allowed for the identification of 49 compounds that had in vitro activity against all four pathogens with minimum inhibitory concentration values of 16 g/mL. Adaptation of the HTS process was necessary to conduct the work in higher-level containment, in this case, biosafety level 3. Examination of chemical scaffolds shared by some of the 49 compounds and assessment of available chemical databases indicates that several may represent broad-spectrum antimicrobials whose activity is based on novel mechanisms of action.
NIAID Category A, B, and C Priority Pathogens. NIAID’s pathogen priority list is periodically reviewed and is subject to revision in conjunction with our federal partners, including the Department of Homeland Security, which determines threat assessments, and the Centers for Disease Control and Prevention (CDC), which is responsible for responding to emerging pathogen threats in the United States.