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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

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 rev...

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Hauptverfasser: López-Cortés, Andrés (VerfasserIn) , Guevara-Ramírez, Patricia (VerfasserIn) , Kyriakidis, Nikolaos C. (VerfasserIn) , Barba-Ostria, Carlos (VerfasserIn) , León Cáceres, Ángela (VerfasserIn) , Guerrero, Santiago (VerfasserIn) , Ortiz-Prado, Esteban (VerfasserIn) , Munteanu, Cristian R. (VerfasserIn) , Tejera, Eduardo (VerfasserIn) , Cevallos-Robalino, Doménica (VerfasserIn) , Gómez-Jaramillo, Ana María (VerfasserIn) , Simbaña-Rivera, Katherine (VerfasserIn) , Granizo-Martínez, Adriana (VerfasserIn) , Pérez-M, Gabriela (VerfasserIn) , Moreno, Silvana (VerfasserIn) , García-Cárdenas, Jennyfer M. (VerfasserIn) , Zambrano, Ana Karina (VerfasserIn) , Pérez-Castillo, Yunierkis (VerfasserIn) , Cabrera-Andrade, Alejandro (VerfasserIn) , Puig San Andrés, Lourdes (VerfasserIn) , Proaño-Castro, Carolina (VerfasserIn) , Bautista, Jhommara (VerfasserIn) , Quevedo, Andreina (VerfasserIn) , Varela, Nelson (VerfasserIn) , Quiñones, Luis Abel (VerfasserIn) , Paz-y-Miño, César (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 26 February 2021
In: Frontiers in pharmacology
Year: 2021, Jahrgang: 12, Pages: 1-24
ISSN:1663-9812
DOI:10.3389/fphar.2021.598925
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3389/fphar.2021.598925
Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/articles/10.3389/fphar.2021.598925/full
Volltext
Verfasserangaben:Andrés López-Cortés, Patricia Guevara-Ramírez, Nikolaos C. Kyriakidis, Carlos Barba-Ostria, Ángela León Cáceres, Santiago Guerrero, Esteban Ortiz-Prado, Cristian R. Munteanu, Eduardo Tejera, Doménica Cevallos-Robalino, Ana María Gómez-Jaramillo, Katherine Simbaña-Rivera, Adriana Granizo-Martínez, Gabriela Pérez-M, Silvana Moreno, Jennyfer M. García-Cárdenas, Ana Karina Zambrano, Yunierkis Pérez-Castillo, Alejandro Cabrera-Andrade, Lourdes Puig San Andrés, Carolina Proaño-Castro, Jhommara Bautista, Andreina Quevedo, Nelson Varela, Luis Abel Quiñones and César Paz-y-Miño
Beschreibung
Zusammenfassung: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 COVID-19 patients. Scripts can be downloaded at https://github.com/muntisa/immuno-drug-repurposing-COVID-19.
Beschreibung:Gesehen am 11.05.2021
Beschreibung:Online Resource
ISSN:1663-9812
DOI:10.3389/fphar.2021.598925

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