TY - JOUR
T1 - LIGHTHOUSE illuminates therapeutics for a variety of diseases including COVID-19
AU - Shimizu, Hideyuki
AU - Kodama, Manabu
AU - Matsumoto, Masaki
AU - Orba, Yasuko
AU - Sasaki, Michihito
AU - Sato, Akihiko
AU - Sawa, Hirofumi
AU - Nakayama, Keiichi I.
N1 - Funding Information:
This work was supported by KAKENHI grants from the Japan Society for the Promotion of Science (JSPS) to H. Shimizu ( JP21K17856 ), M.K. ( JP21K15068 ), and K.I.N. ( JP18H05215 ), as well as by a grant from the Japan Agency for Medical Research and Development (AMED) to K.I.N. ( 21wm0425002 ). H. Shimizu was also supported by postdoctoral fellowships from Takeda Science Foundation and Mochida Foundation . We thank T. Sawada and R. Wada for technical assistance, P.A. Silver and J.C. Way for critical reading of the manuscript, other laboratory members for discussion, and A. Ohta for help with preparation of the manuscript.
Funding Information:
This work was supported by KAKENHI grants from the Japan Society for the Promotion of Science (JSPS) to H. Shimizu (JP21K17856), M.K. (JP21K15068), and K.I.N. (JP18H05215), as well as by a grant from the Japan Agency for Medical Research and Development (AMED) to K.I.N. (21wm0425002). H. Shimizu was also supported by postdoctoral fellowships fromTakeda Science Foundation and Mochida Foundation. We thank T. Sawada and R. Wada for technical assistance, P.A. Silver and J.C. Way for critical reading of the manuscript, other laboratory members for discussion, and A. Ohta for help with preparation of the manuscript. H. S. conceived of and designed the study, developed LIGHTHOUSE, performed validation experiments, and wrote the original draft of the manuscript. M.K. conducted PPAT validation assays. Y.O. M.S. A.S. and H.S. performed COVID-19 infection analyses. M.M. contributed to discussion. K.I.N. supervised the study and edited the manuscript. The authors declare no competing interests.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/11/18
Y1 - 2022/11/18
N2 - 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 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 help accelerate drug discovery and fill the gap between bench side and bedside.
AB - 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 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 help accelerate drug discovery and fill the gap between bench side and bedside.
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U2 - 10.1016/j.isci.2022.105314
DO - 10.1016/j.isci.2022.105314
M3 - Article
AN - SCOPUS:85140300042
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 11
M1 - 105314
ER -
