Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease

• DOI: 10.32920/21950375.v1
• Publication Date: 2023-01-24T19:01:44Z
• Authors: Michael G. Sugiyama; Haotian Cui; Dar’ya S. Redka; Mehran Karimzadeh; Edurne Rujas; Hassaan Maan; Sikander Hayat; Kyle Cheung; Rahul Misra; Joseph McPhee; Russell Viirre; Andrew Haller; Roberto Botelho; Raffi Karshafian; Sarah Sabatinos; Gregory D. Fairn; Seyed Ali Madani ...; Andreas Windemuth; Jean-Philippe Julien; Vijay Shahani; Stephen S. MacKinnon; Bo Wang; Costin N. Antonescu
• Keywords: Drug repositioning; Interactome; Coronavirus; Repurposing; Drug target; Drug Development

<p>The COVID-19 pandemic has highlighted the urgent need for identification of new antiviral drug therapies a variety diseases. is caused by infection with human coronavirus SARS-CoV-2, while other related coronaviruses cause diseases ranging from severe respiratory infections to common cold. We developed computational approach identify targets and repurpose clinically-relevant compounds treatment range Our based on graph convolutional networks (GCN) involves multiscale host-virus interactome analysis coupled off-target predictions. Cell-based experimental assessment reveals several repurposing candidates predicted in silico analyses have activity against infection. In particular, we MET inhibitor capmatinib as having potent broad MET-independent manner, well novel roles host cell proteins such IRAK1/4 supporting infection, which can inform further discovery studies.</p> <p> </p>