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bioRxiv · 10.1101/2021.09.25.461785

LIGHTHOUSE illuminates therapeutics for a variety of diseases including COVID-19

Shimizu, H.·Kodama, M.·Matsumoto, M.·Orba, Y.·Sasaki, M.·Sato, A.·Sawa, H.·Nakayama, K. I.
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Abstract

One of the bottlenecks in the application of basic research findings to patients is the enormous cost, time, and effort required for high-throughput screening of potential drugs for given therapeutic targets. Here we have developed LIGHTHOUSE, a graph-based deep learning approach for discovery of the hidden principles underlying the association of small-molecule compounds with target proteins. Without any 3D structural information for proteins or chemicals, LIGHTHOUSE estimates protein-compound scores that incorporate known evolutionary relations and available experimental data. It identified novel therapeutics for cancer, lifestyle-related disease, and bacterial infection. Moreover, LIGHTHOUSE predicted ethoxzolamide as a therapeutic for coronavirus disease 2019 (COVID-19), and this agent was indeed effective against alpha, beta, gamma, and delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are rampant worldwide. We envision that LIGHTHOUSE will bring about a paradigm shift in translational medicine, providing a bridge from bench side to bedside.

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Shimizu, H., Kodama, M., Matsumoto, M., Orba, Y., Sasaki, M., Sato, A., Sawa, H., Nakayama, K. I.. 2021-09-25. LIGHTHOUSE illuminates therapeutics for a variety of diseases including COVID-19. https://doi.org/10.1101/2021.09.25.461785

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