Integrative Transcriptome Analyses Empower the Anti-COVID-19 Drug Arsenal
Nehme El-Hachem,
Edward Eid,
Georges Nemer,
Ghassan Dbaibo,
Ossama Abbas,
Nelly Rubeiz,
Salah Zeineldine,
Ghassan M. Matar,
Jean-Pierre Bikorimana,
Riam Shammaa,
Benjamin Haibe-Kains,
Mazen Kurban,
Moutih Rafei
Affiliations
Nehme El-Hachem
Faculty of Medicine, Division of Genomics Innovation, American University of Beirut, Lebanon; CHU Sainte-Justine Research Centre, Montreal, Canada; Corresponding author
Edward Eid
Department of Dermatology, American University of Beirut, Lebanon
Georges Nemer
Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
Ghassan Dbaibo
Center for Infectious Diseases Research, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
Ossama Abbas
Department of Dermatology, American University of Beirut, Lebanon
Nelly Rubeiz
Department of Dermatology, American University of Beirut, Lebanon
Salah Zeineldine
American University of Beirut, Department of Internal Medicine, Faculty of Medicine, Beirut, Lebanon
Ghassan M. Matar
Department of Experimental Pathology, Immunology and Microbiology, Center for Infectious Diseases Research, WHO Collaborating Center for Reference & Research on Bacterial Pathogens, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
Jean-Pierre Bikorimana
Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, Canada
Riam Shammaa
Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada; Canadian Centers for Regenerative Therapy, Toronto, ON, Canada; IntelliStem Technologies Inc., Toronto, ON, Canada
Benjamin Haibe-Kains
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Department of Computer Science, University of Toronto, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada; Vector Institute, Toronto, ON, Canada
Mazen Kurban
Department of Dermatology, American University of Beirut, Lebanon; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Corresponding author
Moutih Rafei
Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, Canada; Molecular Biology Program, Université de Montréal, Montreal, QC, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada; Corresponding author
Summary: The beginning of the 21st century has been marked by three distinct waves of zoonotic coronavirus outbreaks into the human population. The COVID-19 (coronavirus disease 2019) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emerged as a global threat endangering the livelihoods of millions worldwide. Currently, and despite collaborative efforts, diverse therapeutic strategies from ongoing clinical trials are still debated. To address the need for such an immediate call of action, we leveraged the largest dataset of drug-induced transcriptomic perturbations, public SARS-CoV-2 transcriptomic datasets, and expression profiles from normal lung transcriptomes. Most importantly, our unbiased systems biology approach prioritized more than 50 repurposable drug candidates (e.g., corticosteroids, Janus kinase and Bruton kinase inhibitors). Further clinical investigation of these FDA-approved candidates as monotherapy or in combination with an antiviral regimen (e.g., remdesivir) could lead to promising outcomes in patients with COVID-19.
