Literature DB >> 33716737

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.

Andrés López-Cortés1,2,3, Patricia Guevara-Ramírez1, Nikolaos C Kyriakidis4, Carlos Barba-Ostria4, Ángela León Cáceres5,6,7, Santiago Guerrero1, Esteban Ortiz-Prado4, Cristian R Munteanu2,8,9, Eduardo Tejera10, Doménica Cevallos-Robalino11, Ana María Gómez-Jaramillo12, Katherine Simbaña-Rivera4, Adriana Granizo-Martínez13, Gabriela Pérez-M14, Silvana Moreno15, Jennyfer M García-Cárdenas1, Ana Karina Zambrano1,8, Yunierkis Pérez-Castillo10, Alejandro Cabrera-Andrade2,10, Lourdes Puig San Andrés1, Carolina Proaño-Castro16, Jhommara Bautista17, Andreina Quevedo1, Nelson Varela3,18, Luis Abel Quiñones3,18, César Paz-Y-Miño1.   

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.
Copyright © 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.

Entities:  

Keywords:  COVID-19; artificial neural networks; drug repurposing; immune system; single-cell RNA sequencing

Year:  2021        PMID: 33716737      PMCID: PMC7952300          DOI: 10.3389/fphar.2021.598925

Source DB:  PubMed          Journal:  Front Pharmacol        ISSN: 1663-9812            Impact factor:   5.810


  151 in total

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Journal:  Nature       Date:  2020-02-03       Impact factor: 69.504

6.  Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.

Authors:  Daniel Wrapp; Nianshuang Wang; Kizzmekia S Corbett; Jory A Goldsmith; Ching-Lin Hsieh; Olubukola Abiona; Barney S Graham; Jason S McLellan
Journal:  Science       Date:  2020-02-19       Impact factor: 47.728

7.  From SARS to COVID-19: A previously unknown SARS- related coronavirus (SARS-CoV-2) of pandemic potential infecting humans - Call for a One Health approach.

Authors:  Mohamed E El Zowalaty; Josef D Järhult
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Authors:  SangJoon Lee; Rudragouda Channappanavar; Thirumala-Devi Kanneganti
Journal:  Trends Immunol       Date:  2020-10-15       Impact factor: 16.687

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Authors:  Andrés López-Cortés; Lavanya Prathap; Esteban Ortiz-Prado; Nikolaos C Kyriakidis; Ángela León Cáceres; Isaac Armendáriz-Castillo; Antonella Vera-Guapi; Verónica Yumiceba; Katherine Simbaña-Rivera; Gabriela Echeverría-Garcés; Jennyfer M García-Cárdenas; Andy Pérez-Villa; Patricia Guevara-Ramírez; Andrea Abad-Sojos; Jhommara Bautista; Lourdes Puig San Andrés; Nelson Varela; Santiago Guerrero
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Journal:  Front Pharmacol       Date:  2022-03-29       Impact factor: 5.810

3.  Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic.

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