A Quantum Similarity Approach for the Discovery of Anti-Trypanosome Drug Leads

DESCRIPTION (provided by applicant): Human African trypanosomiasis (HAT) is an infectious disease with a large global health burden occurring primarily in Central and Eastern Africa. HAT is 100% fatal if untreated and the current drug therapies suffer frompoor safety profiles, difficult treatment regimens, limited effectiveness, and high costs. Furthermore, drugs that cross the blood brain barrier (BBB) are notoriously difficult to develop and have a lower probability of reaching the market place. Here, wepropose to apply a quantum-similarity approach to discover novel T. Brucei inhibitors. The approach allows for simultaneous interrogation of multiple targets and pathways, and for incorporation of various pharmacological requirements early in the discovery process, thus increasing the chances of finding novel therapeutics with great selectivity, potency and pharmacokinetic properties. Instead of screening millions of compounds for novel modulators of the target of interest, our focused testing of 10-2