TY - JOUR
T1 - 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
AU - Lopez-Cortes, Andres
AU - Guevara-Ramirez, Patricia
AU - Kyriakidis, Nikolaos C.
AU - Barba-Ostria, Carlos
AU - Leon Caceres, Angela
AU - Guerrero, Santiago
AU - Ortiz-Prado, Esteban
AU - Munteanu, Cristian R.
AU - Tejera, Eduardo
AU - Cevallos-Robalino, Domenica
AU - Gomez-Jaramillo, Ana Maria
AU - Simbana-Rivera, Katherine
AU - Granizo-Martinez, Adriana
AU - Perez-M, Gabriela
AU - Moreno, Silvana
AU - Garcia-Cardenas, Jennyfer M.
AU - Zambrano, Ana Karina
AU - Perez-Castillo, Yunierkis
AU - Cabrera-Andrade, Alejandro
AU - Puig San Andres, Lourdes
AU - Proano-Castro, Carolina
AU - Bautista, Jhommara
AU - Quevedo, Andreina
AU - Varela, Nelson
AU - Quinones, Luis Abel
AU - Paz-y-Mino, Cesar
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - COVID-19
KW - immune system
KW - single-cell RNA sequencing
KW - artificial neural networks
KW - drug repurposing
KW - COVID-19
KW - immune system
KW - single-cell RNA sequencing
KW - artificial neural networks
KW - drug repurposing
UR - https://res.slu.se/id/publ/111548
U2 - 10.3389/fphar.2021.598925
DO - 10.3389/fphar.2021.598925
M3 - Journal article
SN - 1663-9812
VL - 12
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 598925
ER -