Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches#

Authors#

Niarakis Anna, Ostaszewski Marek, Mazein Alexander, Kuperstein Inna, Kutmon Martina, Gillespie Marc E., Funahashi Akira, Acencio Marcio Luis, Hemedan Ahmed, Aichem Michael, Klein Karsten, Czauderna Tobias, Burtscher Felicia, Yamada Takahiro G., Hiki Yusuke, Hiroi Noriko F., Hu Finterly, Pham Nhung, Ehrhart Friederike, Willighagen Egon L., Valdeolivas Alberto, Dugourd Aurelien, Messina Francesco, Esteban-Medina Marina, Peña-Chilet Maria, Rian Kinza, Soliman Sylvain, Aghamiri Sara Sadat, Puniya Bhanwar Lal, Naldi Aurélien, Helikar Tomáš, Singh Vidisha, Fernández Marco Fariñas, Bermudez Viviam, Tsirvouli Eirini, Montagud Arnau, Noël Vincent, Ponce-de-Leon Miguel, Maier Dieter, Bauch Angela, Gyori Benjamin M., Bachman John A., Luna Augustin, Piñero Janet, Furlong Laura I., Balaur Irina, Rougny Adrien, Jarosz Yohan, Overall Rupert W., Phair Robert, Perfetto Livia, Matthews Lisa, Rex Devasahayam Arokia Balaya, Orlic-Milacic Marija, Gomez Luis Cristobal Monraz, De Meulder Bertrand, Ravel Jean Marie, Jassal Bijay, Satagopam Venkata, Wu Guanming, Golebiewski Martin, Gawron Piotr, Calzone Laurence, Beckmann Jacques S., Evelo Chris T., D’Eustachio Peter, Schreiber Falk, Saez-Rodriguez Julio, Dopazo Joaquin, Kuiper Martin, Valencia Alfonso, Wolkenhauer Olaf, Kitano Hiroaki, Barillot Emmanuel, Auffray Charles, Balling Rudi, Schneider Reinhard, the COVID-19 Disease Map Community

Abstract#

Introduction: The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing.

Methods: Extensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors.

Results: Results revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19.

Discussion: The key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies.