Análisis de las afinidades de unión de la ivermectina, las proteínas nucleocápside y ORF6 del SARS-CoV-2 a las isoformas de las importinas α humanas: Un enfoque computacional
DOI:
https://doi.org/10.18633/biotecnia.v27.2485Palabras clave:
antiparasitario, quimioinformática, carioferinas, proteínas virales, COVID-19Resumen
Se ha demostrado in vitro que la ivermectina reduce la replicación del SARS-CoV-2 en células infectadas mediante la interacción con importinas α, sin embargo, aún se desconoce el mecanismo exacto de acción. El objetivo de este estudio fue analizar afinidades de unión de la ivermectina, la nucleocápside (N) y las proteínas ORF6 del SARS-CoV-2 con isoformas de importinas α humanas utilizando métodos de acoplamiento molecular. Se utilizaron estructuras cristalizadas de importinas α de Protein Data Bank (PDB) y de la AlphaFold Protein Structure Database, y las proteínas virales se modelaron utilizando AlphaFold 2. Se llevaron a cabo simulaciones de acoplamiento molecular entre isoformas de la importina α humana, la ivermectina, y las proteínas N y ORF6, empleando los algoritmos Broy-den-Fletcher-Goldfarb-Shanno, FTDock y pyDockRST. Los datos obtenidos evidenciaron que las proteínas virales del SARS-CoV-2 y la ivermectina presentan afinidades de unión favorables a los dominios ARM2-ARM4 (sitio principal de unión), compartiendo afinidades de interacción con los mismos residuos activos. Estos resultados sugieren que la ivermectina comparte el mismo sitio activo en las importinas α que las proteínas N y ORF6 de SARS-CoV-2, demostrando una potencial diana molecular para la investigación en el desarrollo de nuevos fármacos antivirales contra la COVID-19.
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