Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease
Abstract The COVID-19 pandemic has highlighted the urgent need for the identification of new antiviral drug therapies for a variety of diseases. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2, while other related human coronaviruses cause diseases ranging from severe respirato...
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Nature Portfolio
2021
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oai:doaj.org-article:6fc7b459daf94a499be2325b0bbff79f2021-12-05T12:15:07ZMultiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease10.1038/s41598-021-02432-72045-2322https://doaj.org/article/6fc7b459daf94a499be2325b0bbff79f2021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02432-7https://doaj.org/toc/2045-2322Abstract The COVID-19 pandemic has highlighted the urgent need for the identification of new antiviral drug therapies for a variety of diseases. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2, while other related human coronaviruses cause diseases ranging from severe respiratory infections to the common cold. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of a range of human coronavirus diseases. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cell-based experimental assessment reveals several clinically-relevant drug repurposing 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.Michael G. SugiyamaHaotian CuiDar’ya S. RedkaMehran KarimzadehEdurne RujasHassaan MaanSikander HayatKyle CheungRahul MisraJoseph B. McPheeRussell D. ViirreAndrew HallerRoberto J. BotelhoRaffi KarshafianSarah A. SabatinosGregory D. FairnSeyed Ali Madani TonekaboniAndreas WindemuthJean-Philippe JulienVijay ShahaniStephen S. MacKinnonBo WangCostin N. AntonescuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021) |
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Medicine R Science Q |
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Medicine R Science Q Michael G. Sugiyama Haotian Cui Dar’ya S. Redka Mehran Karimzadeh Edurne Rujas Hassaan Maan Sikander Hayat Kyle Cheung Rahul Misra Joseph B. McPhee Russell D. Viirre Andrew Haller Roberto J. Botelho Raffi Karshafian Sarah A. Sabatinos Gregory D. Fairn Seyed Ali Madani Tonekaboni Andreas Windemuth Jean-Philippe Julien Vijay Shahani Stephen S. MacKinnon Bo Wang Costin N. Antonescu Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease |
| description |
Abstract The COVID-19 pandemic has highlighted the urgent need for the identification of new antiviral drug therapies for a variety of diseases. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2, while other related human coronaviruses cause diseases ranging from severe respiratory infections to the common cold. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of a range of human coronavirus diseases. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cell-based experimental assessment reveals several clinically-relevant drug repurposing 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. |
| format |
article |
| author |
Michael G. Sugiyama Haotian Cui Dar’ya S. Redka Mehran Karimzadeh Edurne Rujas Hassaan Maan Sikander Hayat Kyle Cheung Rahul Misra Joseph B. McPhee Russell D. Viirre Andrew Haller Roberto J. Botelho Raffi Karshafian Sarah A. Sabatinos Gregory D. Fairn Seyed Ali Madani Tonekaboni Andreas Windemuth Jean-Philippe Julien Vijay Shahani Stephen S. MacKinnon Bo Wang Costin N. Antonescu |
| author_facet |
Michael G. Sugiyama Haotian Cui Dar’ya S. Redka Mehran Karimzadeh Edurne Rujas Hassaan Maan Sikander Hayat Kyle Cheung Rahul Misra Joseph B. McPhee Russell D. Viirre Andrew Haller Roberto J. Botelho Raffi Karshafian Sarah A. Sabatinos Gregory D. Fairn Seyed Ali Madani Tonekaboni Andreas Windemuth Jean-Philippe Julien Vijay Shahani Stephen S. MacKinnon Bo Wang Costin N. Antonescu |
| author_sort |
Michael G. Sugiyama |
| title |
Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease |
| title_short |
Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease |
| title_full |
Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease |
| title_fullStr |
Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease |
| title_full_unstemmed |
Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease |
| title_sort |
multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/6fc7b459daf94a499be2325b0bbff79f |
| work_keys_str_mv |
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