AUTHOR=López-Cortés Andrés , Guevara-Ramírez Patricia , Kyriakidis Nikolaos C. , Barba-Ostria Carlos , León Cáceres Ángela , Guerrero Santiago , Ortiz-Prado Esteban , Munteanu Cristian R. , Tejera Eduardo , Cevallos-Robalino Doménica , Gómez-Jaramillo Ana María , Simbaña-Rivera Katherine , Granizo-Martínez Adriana , Pérez-M Gabriela , Moreno Silvana , García-Cárdenas Jennyfer M. , Zambrano Ana Karina , Pérez-Castillo Yunierkis , Cabrera-Andrade Alejandro , Puig San Andrés Lourdes , Proaño-Castro Carolina , Bautista Jhommara , Quevedo Andreina , Varela Nelson , Quiñones Luis Abel , Paz-y-Miño César 

TITLE=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

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.598925

DOI=10.3389/fphar.2021.598925

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> There is pressing urgency to identify therapeutic targets and drugs that allow treating COVID-19 patients effectively.</p><p><bold>Methods:</bold> We performed <italic>in silico</italic> 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.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusion:</bold> After being effectively analyzed in clinical trials, these drugs can be considered for treatment of severe COVID-19 patients. Scripts can be downloaded at <ext-link ext-link-type="uri" xlink:href="https://github.com/muntisa/immuno-drug-repurposing-COVID-19" xmlns:xlink="http://www.w3.org/1999/xlink">https://github.com/muntisa/immuno-drug-repurposing-COVID-19</ext-link>.</p>