Schistosomiasis, also known as snail fever, is a parasitic disease caused by the Schistosoma blood fluke that infects humans when freshwater snail larvae penetrate the skin. Although the worm itself is not found in the United States, the disease affects an estimated 240 million people worldwide and the only drug currently available for treatment is praziquantel (PZQ). Considering the possibility of resistance and the pharmacological and pharmaceutical drawbacks of PZQ, new treatments are needed. Sharing data and ideas is an important obstacle to overcome when developing any treatment, but particularly for neglected tropical diseases (NTDs) such as this, as experts are scattered globally and communication is limited.<br/>Assay Central facilitates drug discovery collaboration by deploying a collection of predictive Bayesian models in a self-contained executable. Datasets of structure-activity relationships are collated and stored using the code-management system Git, from which molecular descriptors (extended-connectivity fingerprints) are calculated as contributing to activity against disease targets. Novel molecules are assigned a score reflecting predicted activity against a target of interest, while visualization of molecular features and training data solidify comprehension and compliment human intuition to make intelligent decisions.<br/>Models of anti-schistosomiasis activity were created specific to time-point (from 1-6 days) and worm life stage (somule/larva or adult), initially from Caffrey group data only, but later from published data. Compounds are periodically selected for testing using these models and results are integrated appropriately. Somule models have larger datasets and cover a wider chemical space, but adult worm models have been bolstered with more published data. For all models, Receiver Operator Characteristic scores ranged from 0.58-0.80. A feedback loop of this nature can improve model predictions and drive drug discovery for NTDs, and Assay Central can reduce superfluous synthesis and testing by driving discussion between collaborators.

Drug repurposing for schistosomiasis with assay central

256th National Meeting (2018)

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