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Integrative Transcriptome Analyses Empower the Anti-COVID-19 Drug Arsenal

35 Pages Posted: 20 Jul 2020 Publication Status: Published

See all articles by Nehme El Hachem

Nehme El Hachem

Independent

Edward Eid

Independent

Georges Nemer

Independent

Ghassan Dbaibo

Independent

Ossama Abbas

Independent

Nelly Rubeiz

Independent

Salah Zeineldine

Independent

Ghassan M. Matar

Independent

Jean-Pierre Bikorimana

Independent

Riam Shammaa

University of Toronto - Department of Family and Community Medicine

Benjamin Haibe-Kains

Independent

Mazen Kurban

Independent

Moutih Rafei

University of Montreal - Department of Pharmacology and Physiology

More...

Abstract

The beginning of the twenty-first century has been marked by three distinct waves of zoonotic coronavirus outbreaks into the human population. The current pandemic COVID-19 (Coronavirus disease 2019) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a rapid infection rate, it is a global threat endangering the livelihoods of millions worldwide. Currently, and despite the collaborative efforts of governments, researchers, and the pharmaceutical industries, there are no substantially significant treatment protocols for the disease. 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. Our unbiased systems biology approach not only shed light on previously unexplored molecular details of SARS-CoV-2 infection (e.g., interferon signaling, inflammation and ACE2 co-expression hallmarks in normal and infected lungs) but most importantly 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 COVID-19 patients.

Funding: This work is partially supported by a Discovery Grant from the National Sciences and Engineering Research Council of Canada (RGPIN/06101-2014) and an operating grant from the Cancer Research Society (OG24054). M.R holds a Fonds de la Recherche en Santé du Québec Junior II Award.

Conflict of Interest: All authors declare no conflict of interest.

Suggested Citation

El Hachem, Nehme and Eid, Edward and Nemer, Georges and Dbaibo, Ghassan and Abbas, Ossama and Rubeiz, Nelly and Zeineldine, Salah and M. Matar, Ghassan and Bikorimana, Jean-Pierre and Shammaa, Riam and Haibe-Kains, Benjamin and Kurban, Mazen and Rafei, Moutih, Integrative Transcriptome Analyses Empower the Anti-COVID-19 Drug Arsenal. Available at SSRN: https://ssrn.com/abstract=3653546 or http://dx.doi.org/10.2139/ssrn.3653546
This version of the paper has not been formally peer reviewed.

Edward Eid

Independent ( email )

Georges Nemer

Independent ( email )

Ghassan Dbaibo

Independent ( email )

Ossama Abbas

Independent ( email )

Nelly Rubeiz

Independent ( email )

Salah Zeineldine

Independent ( email )

Ghassan M. Matar

Independent ( email )

Jean-Pierre Bikorimana

Independent ( email )

Riam Shammaa

University of Toronto - Department of Family and Community Medicine ( email )

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

Benjamin Haibe-Kains

Independent ( email )

Mazen Kurban

Independent ( email )

Moutih Rafei

University of Montreal - Department of Pharmacology and Physiology ( email )

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

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