High-throughput screening (HTS) of libraries with large numbers of small molecules is a widely recognized and increasingly used method for identifying compounds that modulate biological processes. Compounds thus identified can be powerful molecular probes for dissecting complex biological pathways, and may also be potential leads for clinical use. In the context of biodefense and emerging infectious disease, small molecule HTS could lead to the discovery of new classes of antimicrobial agents or novel stimulators of innate or adaptive immunity, and also identify and validate novel targets for subsequent drug discovery efforts. The National Small Molecule Screening Laboratory for the RCEs in Biodefense and Emerging Infectious Disease (NSRB) was established in 2003 to provide access to small molecule high-throughput screening (HTS) and medicinal chemistry resources for all U.S. investigators conducting research on NIAID Priority Pathogens. It has been a highly successful program and several NSRB projects have produced reagents that are progressing toward possible therapeutic development. The NERCE National Small Molecule Screening and Medicinal Chemistry Core (Core C) propsed here is a continuation of the NSRB. The main goals for Core C are to: Provide access to small-molecule HTS for all U.S. investigators with projects focused on NIAID Priority Pathogens and agents of Emerging Infectious Diseases, and to Provide data analysis and medicinal chemistry resources for maturation of screening positives into smallmolecule research tools or into potential novel therapeutic leads.

Public Health Relevance

Small molecule screening is an important method for identifying agents that affect biological processes and can be applied to the study of infectious disease. Agents discovered by small molecule screening might eventually be developed as therapeutics to treat or prevent microbial infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI057159-07
Application #
8038346
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
7
Fiscal Year
2010
Total Cost
$959,704
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
de Wispelaere, Melissanne; Lian, Wenlong; Potisopon, Supanee et al. (2018) Inhibition of Flaviviruses by Targeting a Conserved Pocket on the Viral Envelope Protein. Cell Chem Biol 25:1006-1016.e8
Huang, Nai-Jia; Pishesha, Novalia; Mukherjee, Jean et al. (2017) Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin. Nat Commun 8:423
Mertins, Philipp; Przybylski, Dariusz; Yosef, Nir et al. (2017) An Integrative Framework Reveals Signaling-to-Transcription Events in Toll-like Receptor Signaling. Cell Rep 19:2853-2866
Nair, Dhanalakshmi R; Chen, Ji; Monteiro, João M et al. (2017) A quinolinol-based small molecule with anti-MRSA activity that targets bacterial membrane and promotes fermentative metabolism. J Antibiot (Tokyo) 70:1009-1019
Choo, Min-Kyung; Sano, Yasuyo; Kim, Changhoon et al. (2017) TLR sensing of bacterial spore-associated RNA triggers host immune responses with detrimental effects. J Exp Med 214:1297-1311
de Wispelaere, Mélissanne; Carocci, Margot; Liang, Yanke et al. (2017) Discovery of host-targeted covalent inhibitors of dengue virus. Antiviral Res 139:171-179
Umetsu, Dale T (2017) Mechanisms by which obesity impacts upon asthma. Thorax 72:174-177
Zheng, Huiqing; Colvin, Christopher J; Johnson, Benjamin K et al. (2017) Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence. Nat Chem Biol 13:218-225
Coulson, Garry B; Johnson, Benjamin K; Zheng, Huiqing et al. (2017) Targeting Mycobacterium tuberculosis Sensitivity to Thiol Stress at Acidic pH Kills the Bacterium and Potentiates Antibiotics. Cell Chem Biol 24:993-1004.e4
Böttcher, Thomas; Elliott, Hunter L; Clardy, Jon (2016) Dynamics of Snake-like Swarming Behavior of Vibrio alginolyticus. Biophys J 110:981-92

Showing the most recent 10 out of 417 publications