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Viruses ; 13(8)2021 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-34452405

RESUMEN

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico-informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, "Adrenergic receptor antagonist", "ATPase inhibitor", "NF-kB pathway inhibitor" and "Serotonin receptor antagonist", were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.


Asunto(s)
Antivirales/uso terapéutico , Dengue/tratamiento farmacológico , Transcriptoma , Adenosina Trifosfatasas/antagonistas & inhibidores , Antagonistas Adrenérgicos/farmacología , Antagonistas Adrenérgicos/uso terapéutico , Antivirales/farmacología , Encéfalo/metabolismo , Simulación por Computador , Dengue/sangre , Dengue/genética , Dengue/metabolismo , Descubrimiento de Drogas , Evaluación Preclínica de Medicamentos , Reposicionamiento de Medicamentos , Humanos , Hígado/metabolismo , Redes y Vías Metabólicas/efectos de los fármacos , FN-kappa B/metabolismo , Antagonistas de la Serotonina/farmacología , Antagonistas de la Serotonina/uso terapéutico , Dengue Grave/sangre , Dengue Grave/tratamiento farmacológico , Dengue Grave/genética , Dengue Grave/metabolismo , Bazo/metabolismo
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