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

López-Cortés, AndrésGuevara-Ramírez, PatriciaKyriakidis, Nikolaos C.Barba-Ostria, CarlosLeón Cáceres, ÁngelaGuerrero, SantiagoOrtiz-Prado, EstebanMunteanu, Cristian-RobertTejera, EduardoCevallos-Robalino, DoménicaGómez-Jaramillo, Ana MaríaSimbaña-Rivera, KatherineGranizo-Martínez, AdrianaPérez-M, GabrielaMoreno, SilvanaGarcía-Cárdenas, Jennyfer M.Zambrano, Ana KarinaPérez-Castillo, YunierkisCabrera-Andrade, AlejandroPuig San Andrés, LourdesProaño-Castro, CarolinaBautista, JhommaraQuevedo, AndreinaVarela, NelsonQuiñones, Luis AbelPaz-y-Miño, César2021-04-232021-04-232021-02-26López-Cortés A, Guevara-Ramírez P, Kyriakidis NC, Barba-Ostria C, León Cáceres Á, Guerrero S, Ortiz-Prado E, Munteanu CR, Tejera E, Cevallos-Robalino D, Gómez-Jaramillo AM, Simbaña-Rivera K, Granizo-Martínez A, Pérez-M G, Moreno S, García-Cárdenas JM, Zambrano AK, Pérez-Castillo Y, Cabrera-Andrade A, Puig San Andrés L, Proaño-Castro C, Bautista J, Quevedo A, Varela N, Quiñones LA and Paz-y-Miño C (2021) 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. Front. Pharmacol. 12:598925. doi: 10.3389/fphar.2021.5989251663-9812http://hdl.handle.net/2183/27803[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.engAtribución 4.0 InternacionalCopyright © 2021 López-Cortés, Guevara-Ramírez, Kyriakidis, Barba-Ostria, León Cáceres, Guerrero, Ortiz-Prado, Munteanu, Tejera, Cevallos-Robalino, Gómez- Jaramillo, Simbaña-Rivera, Granizo-Martínez, Pérez-M, Moreno, García- Cárdenas, Zambrano, Pérez-Castillo, Cabrera-Andrade, Puig San Andrés, Proaño-Castro, Bautista, Quevedo, Varela, Quiñones and Paz-y-Miño. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.http://creativecommons.org/licenses/by/4.0/COVID-19Immune systemSingle-cell RNA sequencingArtificial neural networksDrug repurposingIn 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-19journal articleopen access10.3389/fphar.2021.598925