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

Hideyuki Shimizu; Manabu Kodama; Masaki Matsumoto; Yasuko Orba; Michihito Sasaki; Akihiko Sato; Hirofumi Sawa; Keiichi I. Nakayama

iScience (Nov 2022)

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

Hideyuki Shimizu,
Manabu Kodama,
Masaki Matsumoto,
Yasuko Orba,
Michihito Sasaki,
Akihiko Sato,
Hirofumi Sawa,
Keiichi I. Nakayama

Affiliations

Hideyuki Shimizu: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Wyss Institute for Biologically Inspired Engineering, Harvard Medical School, Boston, MA 02115, USA; Department of AI Systems Medicine, M&D Data Science Center, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; Corresponding author
Manabu Kodama: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
Masaki Matsumoto: Department of Omics and Systems Biology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Yasuko Orba: Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 060-8638, Japan
Michihito Sasaki: Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 060-8638, Japan
Akihiko Sato: Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 060-8638, Japan; Drug Discovery and Disease Research Laboratory, Shionogi & Co. Ltd., Osaka 561-0825, Japan
Hirofumi Sawa: Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 060-8638, Japan; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo 060-8638, Japan; One Health Research Center, Hokkaido University, Sapporo 060-8638, Japan; Global Virus Network, Baltimore, MD 21201, USA; Hokkaido University, Institute for Vaccine Research and Development (HU-IVReD)
Keiichi I. Nakayama: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Corresponding author

Journal volume & issue: Vol. 25, no. 11
p. 105314

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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