RESUMEN
The natural pathway of antioxidant production is mediated through Kelch-like erythroid cell-derived protein with Cap and collar homology [ECH]-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2) system. Keap1 maintains a low level of Nrf2 by holding it in its protein complex. Also, Keap1 facilitates the degradation of Nrf2 by ubiquitination. In other words, Keap1 is a down-regulator of Nrf2. To boost the production of biological antioxidants, Keap1 has to be inhibited and Nrf2 has to be released. Liberated Nrf2 is in an unbound state, so it travels to the nucleus to stimulate the antioxidant response element (ARE) present on the antioxidant genes. AREs activate biosynthesis of biological antioxidants through genes responsible for the production of antioxidants. In some cases of coronavirus disease 2019 (COVID-19), there is an enormous release of cytokines. The antioxidant defense mechanism in the body helps in counteracting symptoms induced by the cytokine storm in COVID-19. So, boosting the production of antioxidants is highly desirable in such a condition. In this review article, we have compiled the role of Keap1-Nrf2 system in antioxidant production. We further propose its potential therapeutic use in managing cytokine storm in COVID-19.
Asunto(s)
COVID-19/metabolismo , COVID-19/terapia , Síndrome de Liberación de Citoquinas/metabolismo , Síndrome de Liberación de Citoquinas/terapia , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Manejo de la Enfermedad , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/antagonistas & inhibidores , Factor 2 Relacionado con NF-E2/agonistas , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiologíaAsunto(s)
Tratamiento Farmacológico de COVID-19 , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Ácido Oleanólico/análogos & derivados , SARS-CoV-2/enzimología , Antivirales/química , COVID-19/enzimología , COVID-19/virología , Química Computacional , Proteasas 3C de Coronavirus/química , Reposicionamiento de Medicamentos , Humanos , Factor 2 Relacionado con NF-E2/agonistas , Factor 2 Relacionado con NF-E2/química , Ácido Oleanólico/química , Inhibidores de Proteasas/química , Inhibidores de Proteasas/uso terapéutico , SARS-CoV-2/patogenicidad , Replicación Viral/efectos de los fármacosRESUMEN
COVID-19 is a severe pandemic which has caused a devastating amount of loss in lives around the world, and yet we still don't know how to appropriately treat this disease. We know very little about the pathogenesis of SARS-CoV-2, the virus which induces the COVID-19. However, COVID-19 does share many similar symptoms with SARS and influenza. Previous scientific discoveries learned from lab animal models and clinical practices shed light on possible pathogenic mechanisms in COVID-19. In the past decades, accumulated scientific findings confirmed the pathogenic role of free radicals damage in respiratory virus infection. Astonishingly very few medical professionals mention the crucial role of free radical damage in COVID-19. This hypothesis aims to summarize the crucial pathogenic role of free radical damage in respiratory virus induced pneumonia and suggest an antioxidative therapeutic strategy for COVID-19.