In silico Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19
Open Access
- 26 February 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Pharmacology
- Vol. 12, 598925
- https://doi.org/10.3389/fphar.2021.598925
Abstract
Background: There is pressing urgency to identify therapeutic targets and drugs that allow treating COVID-19 patients effectively. Methods: We performed in silico analyses of immune system protein interactome network, single-cell RNA sequencing of human tissues, and artificial neural networks to reveal potential therapeutic targets for drug repurposing against COVID-19. Results: We screened 1,584 high-confidence immune system proteins in ACE2 and TMPRSS2 co-expressing cells, finding 25 potential therapeutic targets significantly overexpressed in nasal goblet secretory cells, lung type II pneumocytes, and ileal absorptive enterocytes of patients with several immunopathologies. Then, we performed fully connected deep neural networks to find the best multitask classification model to predict the activity of 10,672 drugs, obtaining several approved drugs, compounds under investigation, and experimental compounds with the highest area under the receiver operating characteristics. Conclusion: After being effectively analyzed in clinical trials, these drugs can be considered for treatment of severe COVID-19 patients. Scripts can be downloaded at https://github.com/muntisa/immuno-drug-repurposing-COVID-19.This publication has 189 references indexed in Scilit:
- InnateDB: systems biology of innate immunity and beyond—recent updates and continuing curationNucleic Acids Research, 2012
- Viral Perturbations of Host Networks Reflect Disease EtiologyPLoS Computational Biology, 2012
- Securing the public good of health research and development for developing countriesBulletin of the World Health Organization, 2012
- Interactome Networks and Human DiseaseCell, 2011
- Systematic and integrative analysis of large gene lists using DAVID bioinformatics resourcesNature Protocols, 2008
- Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene listsNucleic Acids Research, 2008
- IMGT(R), the international ImMunoGeneTics information system(R)Nucleic Acids Research, 2008
- Hepatitis C virus infection protein networkMolecular Systems Biology, 2008
- Epstein–Barr virus and virus human protein interaction mapsProceedings of the National Academy of Sciences of the United States of America, 2007
- Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction NetworksGenome Research, 2003