In silico drug repurposing in COVID-19: A network-based analysis

• Published in: Biomedicine & pharmacotherapy Vol. 142; p. 111954
• Main Authors: Sibilio, Pasquale, Bini, Simone, Fiscon, Giulia, Sponziello, Marialuisa, Conte, Federica, Pecce, Valeria, Durante, Cosimo, Paci, Paola, Falcone, Rosa, Norata, Giuseppe Danilo, Farina, Lorenzo, Verrienti, Antonella
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.10.2021; The Authors. Published by Elsevier Masson SAS
• Subjects: Anti-Inflammatory Agents - pharmacology; Central Nervous System Agents - pharmacology; Computer Simulation; Corticosteroid; COVID-19; COVID-19 - prevention & control; COVID-19 Drug Treatment; Drug Repositioning - methods; Drug Repositioning - trends; Drug repurposing; Enzyme Inhibitors - pharmacology; Gene Expression Profiling - methods; Heparin; Humans; Immunologic Factors - pharmacology; Inflammatory bowel disease; Septic shock; Treatment Outcome; Voltage-Gated Sodium Channel Blockers - pharmacology; COVID-19; Inflammatory bowel disease; Drug repurposing; Corticosteroid; Septic shock; Heparin
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2021.111954

The SARS-CoV-2 pandemic is a worldwide public health emergency. Despite the beginning of a vaccination campaign, the search for new drugs to appropriately treat COVID-19 patients remains a priority. Drug repurposing represents a faster and cheaper method than de novo drug discovery. In this study, we examined three different network-based approaches to identify potentially repurposable drugs to treat COVID-19. We analyzed transcriptomic data from whole blood cells of patients with COVID-19 and 21 other related conditions, as compared with those of healthy subjects. In addition to conventionally used drugs (e.g., anticoagulants, antihistaminics, anti-TNFα antibodies, corticosteroids), unconventional candidate compounds, such as SCN5A inhibitors and drugs active in the central nervous system, were identified. Clinical judgment and validation through clinical trials are always mandatory before use of the identified drugs in a clinical setting. [Display omitted] •Drug repurposing based on network medicine approach identified new drugs for COVID-19.•SAveRUNNER identified drugs acting on targets within or next to COVID-19 module.•Network-based separation measure found disease modules close to COVID-19 module.•Random walk with restart identified diseases whose drugs may perturb the COVID-19 module.•Interesting identified drugs are active in the CNS and other are antiarrhythmic agents.