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. 1. Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador. 2. RNASA-IMEDIR, Computer Science Faculty, University of A Coruna, A Coruña, Spain. 3. Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Madrid, Spain. 4. One Health Research Group, Faculty of Medicine, Universidad de Las Américas (UDLA), Quito, Ecuador. 5. Heidelberg Institute of Global Health, Faculty of Medicine, Heidelberg University, Heidelberg, Germany. 6. Instituto de Salud Pública, Facultad de Medicina, Pontificia Universidad Católica del Ecuador, Quito, Ecuador. 7. Tropical Herping, Quito, Ecuador. 8. Biomedical Research Institute of A Coruna (INIBIC), University Hospital Complex of A Coruna (CHUAC), A Coruña, Spain. 9. Centro de Información en Tecnologías de la Información y las Comunicaciones (CITIC), A Coruña, Spain. 10. Grupo de Bio-Quimioinformática, Universidad de Las Américas (UDLA), Quito, Ecuador. 11. Hospital General del Sur de Quito, Instituto Ecuatoriano de Seguridad Social, Quito, Ecuador. 12. Faculty of Medicine, Pontifical Catholic University of Ecuador, Quito, Ecuador. 13. Carrera de Medicina, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador. 14. Centro Clínico Quirúrgico Ambulatorio Hospital del Día El Batán, Instituto Ecuatoriano de Seguridad Social, Quito, Ecuador. 15. Department of Plant Biology, Faculty of Natural Resources and Agricultural Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden. 16. Fundación Futuro, Quito, Ecuador. 17. Facultad de Ingeniería y Ciencias Aplicadas-Biotecnología, Universidad de Las Américas, Quito, Ecuador. 18. Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile, Santiago, Chile.
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.
Background: There is pressing urgency to identify therapeutic targets and drugs that allow treating COVID-19patients 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-19patients. Scripts can be downloaded at https://github.com/muntisa/immuno-drug-repurposing-COVID-19.
Authors: Jose Ordovas-Montanes; Daniel F Dwyer; Sarah K Nyquist; Kathleen M Buchheit; Marko Vukovic; Chaarushena Deb; Marc H Wadsworth; Travis K Hughes; Samuel W Kazer; Eri Yoshimoto; Katherine N Cahill; Neil Bhattacharyya; Howard R Katz; Bonnie Berger; Tanya M Laidlaw; Joshua A Boyce; Nora A Barrett; Alex K Shalek Journal: Nature Date: 2018-08-22 Impact factor: 49.962
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
Authors: Andrés López-Cortés; Santiago Guerrero; Esteban Ortiz-Prado; Verónica Yumiceba; Antonella Vera-Guapi; Ángela León Cáceres; Katherine Simbaña-Rivera; Ana María Gómez-Jaramillo; Gabriela Echeverría-Garcés; Jennyfer M García-Cárdenas; Patricia Guevara-Ramírez; Alejandro Cabrera-Andrade; Lourdes Puig San Andrés; Doménica Cevallos-Robalino; Jhommara Bautista; Isaac Armendáriz-Castillo; Andy Pérez-Villa; Andrea Abad-Sojos; María José Ramos-Medina; Ariana León-Sosa; Estefanía Abarca; Álvaro A Pérez-Meza; Karol Nieto-Jaramillo; Andrea V Jácome; Andrea Morillo; Fernanda Arias-Erazo; Luis Fuenmayor-González; Luis Abel Quiñones; Nikolaos C Kyriakidis Journal: Front Pharmacol Date: 2022-03-29 Impact factor: 5.810