@article {Sugiyama2021.04.13.439274, author = {Michael G. Sugiyama and Haotian Cui and Dar{\textquoteright}ya S. Redka and Mehran Karimzadeh and Edurne Rujas and Hassaan Maan and Sikander Hayat and Kyle Cheung and Rahul Misra and Joseph B. McPhee and Russell D. Viirre and Andrew Haller and Roberto J. Botelho and Raffi Karshafian and Sarah A. Sabatinos and Gregory D. Fairn and Seyed Ali Madani Tonekaboni and Andreas Windemuth and Jean-Philippe Julien and Vijay Shahani and Stephen S. MacKinnon and Bo Wang and Costin N. Antonescu}, title = {Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease}, elocation-id = {2021.04.13.439274}, year = {2021}, doi = {10.1101/2021.04.13.439274}, publisher = {Cold Spring Harbor Laboratory}, abstract = {The COVID-19 pandemic has led to an urgent need for the identification of new antiviral drug therapies that can be rapidly deployed to treat patients with this disease. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of COVID-19. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cellbased experimental assessment reveals several clinically-relevant repurposing drug candidates predicted by the in silico analyses to have antiviral activity against human coronavirus infection. In particular, we identify the MET inhibitor capmatinib as having potent and broad antiviral activity against several coronaviruses in a MET-independent manner, as well as novel roles for host cell proteins such as IRAK1/4 in supporting human coronavirus infection, which can inform further drug discovery studies.Competing Interest StatementDSR, SAMT, AW, VS, SSM are employees of Cyclica Inc, and may own stock in Cyclica Inc. SH is an employee of Bayer US LLC (a subsidiary of Bayer AG) and may own stock in Bayer AG. AH is founder and CEO of Phoenox Pharma and may own stocks in Phoenox Pharma. CNA, RK and RDV serve on the scientific advisory board of Phoenox Pharma. All other authors declare no competing interests.}, URL = {https://www.biorxiv.org/content/early/2021/04/13/2021.04.13.439274}, eprint = {https://www.biorxiv.org/content/early/2021/04/13/2021.04.13.439274.full.pdf}, journal = {bioRxiv} }