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

Anna Niarakis (1, 2) , Marek Ostaszewski (3) , Alexander Mazein (3) , Inna Kuperstein (4, 5) , Martina Kutmon (6) , Marc E Gillespie (7) , Akira Funahashi (8) , Marcio Luis Acencio (3) , Ahmed Hemedan (9) , Michael Aichem (10) , Karsten Klein (11) , Tobias Czauderna (12) , Felicia Burtscher (3) , Takahiro G Yamada , Yusuke Hiki (8) , Noriko F Hiroi , Finterly Hu (6) , Nhung Pham (6) , Friederike Ehrhart (13) , Egon L Willighagen (13) , Alberto Valdeolivas (14) , Aurelien Dugourd (14) , Francesco Messina (15) , Marina Esteban-Medina (16, 17) , Maria Peña-Chilet (16, 17) , Kinza Rian (16, 17) , Sylvain Soliman (2) , Sara Sadat Aghamiri (18) , Bhanwar Lal Puniya (18) , Aurélien Naldi (2) , Vidisha Singh (1) , Viviam Bermudez (19) , Eirini Tsirvouli (19) , Arnau Montagud (20) , Vincent Noël (21) , Miguel Ponce-De-Leon (20) , Dieter Maier (22) , Angela Bauch (22) , Benjamin M Gyori (23) , John A Bachman (23) , Augustin Luna (23) , Janet Piñero (24) , Laura I Furlong (24) , Irina Balaur (3) , Adrien Rougny (25) , Yohan Jarosz (3) , Rupert W Overall (26) , Robert Phair (27) , Livia Perfetto (28) , Lisa Matthews (29) , Devasahayam Arokia (30) , Balaya Rex , Marija Orlic-Milacic (7) , Cristobal Luis (31) , Bertrand de Meulder (32) , Jean Marie Ravel (31) , Bijay Jassal (7) , Venkata Satagopam (33) , Guanming Wu (34) , Martin Golebiewski (35) , Piotr Gawron (3) , Laurence Calzone (31) , Jacques S Beckmann (36) , Chris T Evelo (37) , Peter d'Eustachio (29) , Falk Schreiber (38) , Julio Saez-Rodriguez (39) , Joaquin Dopazo (17, 40, 16) , Martin Kuiper (41) , Alfonso Valencia (20) , Olaf Wolkenhauer (42, 43) , Hiroaki Kitano (44) , Emmanuel Barillot (31) , Charles Auffray (32) , Rudi Balling (45) , Reinhard Schneider (3) , Issam El Naqa , Stefano Casarin , Marcus Scotti , Gillespie Me , Acencio Ml , Czauderna T Burtscher , Yamada Tg , Hiroi Nf , Willighagen El , Aghamiri Ss , Puniya Bl , V Mf, Bermudez , Gyori Bm , Bachman Ja , Virgen del Rocı

1 GenHotel - Laboratoire de recherche européen pour la polyarthrite rhumatoïde
2 Lifeware - Computational systems biology and optimization
3 University of Luxembourg [Luxembourg]
4 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
5 PSL - Université Paris Sciences et Lettres
6 MaCSBio - Maastricht Centre for Systems Biology [Maastricht]
7 OICR - Ontario Institute for Cancer Research [Canada]
8 Keio University [Tokyo]
9 LCSB - Luxembourg Centre For Systems Biomedicine
10 University of Konstanz
11 Universität Konstanz
12 Hochschule Mittweida - University of Applied Sciences
13 Maastricht University [Maastricht]
14 Heidelberg University Hospital [Heidelberg]
15 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
16 Hospital Universitario Virgen del Rocío [Sevilla]
17 Biomedicine Institute of Sevilla [Seville, Spain]
18 University of Nebraska–Lincoln
19 NTNU - Norwegian University of Science and Technology [Trondheim]
20 BSC-CNS - Barcelona Supercomputing Center - Centro Nacional de Supercomputacion
21 SLAC - SLAC National Accelerator Laboratory
22 Biomax Informatics [Planegg]
23 HMS - Harvard Medical School [Boston]
24 UPF - Universitat Pompeu Fabra [Barcelona]
25 AIST - National Institute of Advanced Industrial Science and Technology
26 HU Berlin - Humboldt-Universität zu Berlin = Humboldt University of Berlin = Université Humboldt de Berlin
27 Integrative Bioinformatics Inc [Mountain View]
28 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
29 NYU Langone Medical Center - New York University Langone Medical Center
30 Yenepoya University
31 INSERM - Institut National de la Santé et de la Recherche Médicale
32 EISBM - European Institute for Systems Biology and Medicine
33 Goethe-Universität Frankfurt am Main
34 OSU - Oregon State University
35 HITS - Heidelberg Institute for Theoretical Studies
36 UNIL - Université de Lausanne = University of Lausanne
37 BigCat - Bioinformatics and Systems Biology Research Group
38 Monash University [Clayton]
39 Universität Heidelberg [Heidelberg] = Heidelberg University
40 CIBER de Enfermedades Raras (CIBERER)
41 NTNU - Norwegian University of Science and Technology
42 University of Rostock
43 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
44 SBI - The Systems Biology Institute [Tokyo]
45 Universität Bonn = University of Bonn

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.

Domains: Life Sciences [q-bio]; Bioinformatics [q-bio.QM]

Anna Niarakis, Marek Ostaszewski, Alexander Mazein, Inna Kuperstein, Martina Kutmon, et al.. Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches. Frontiers in Immunology, 2024, 14, ⟨10.3389/fimmu.2023.1282859⟩. ⟨hal-04454379⟩