Análisis de los sitios de unión de la ivermectina en la estructura de importinas α humanas: Sitios de unión de la ivermectina en importinas α

Elvio Gayozo; Laura Rojas Aguadé; Julio Barrios Leiva

doi:10.47993/gmb.v47i1.791

Autores/as

Elvio Gayozo Universidad Nacional de Asunción, Facultad de Ciencias Exactas y Naturales, Departamento de Biología, San Lorenzo, Paraguay
Laura Rojas Aguadé Universidad Nacional de Asunción, Facultad de Ciencias Químicas, Departamento de Microbiología Industrial, San Lorenzo, Paraguay
Julio Barrios Leiva Universidad Nacional de Asunción, Facultad de Ciencias Exactas y Naturales, Departamento de Biotecnología, San Lorenzo, Paraguay

DOI:

https://doi.org/10.47993/gmb.v47i1.791

Palabras clave:

Antiparasitario, carioferinas, dominio proteico, biología computacional

Resumen

Resumen: La ivermectina ha demostrado importantes actividades antivirales in vitro contra numerosos virus de ARN, inclusive contra el virus del SARS-CoV-2. Se ha descrito que la ivermectina inhibe la actividad del heterodímero importina α/β1, sin embargo, se desconoce los sitios específicos blancos de interacción de la molécula.

Objetivos: En este estudio se llevó a cabo el análisis in silico de los sitios de unión de la molécula de ivermectina en interacción con la estructura de la importina α humana, utilizando la estrategia del acoplamiento molecular.

Métodos: Se realizaron simulaciones del acoplamiento utilizando un modelo semiflexible y el algoritmo Broyden-Fletcher-Goldfarb-Shanno entre las estructuras de ivermectina y la importina α.

Resultados: Los datos obtenidos revelan una mayor afinidad de interacción de la ivermectina en los dominios ARM2-ARM4 (sitio mayor de unión) de las importinas α humanas, con energías de unión favorables de -9,5 a -8,0 kcal.mol^-1. Los residuos activos de mayor importancia en las interacciones fueron los residuos Triptófano, Asparagina y Arginina, los cuales también son fundamentales para el reconocimiento de secuencias NLS (secuencias de localización nuclear) de las proteínas virales. También se registró afinidades por los dominios H1-ARM5, H2-ARM6 y H2-ARM7, con energía de unión de -7,5 kcal.mol^-1.

Conclusiones: Los resultados de este estudio evidencian que la molécula de ivermectina presenta afinidades de unión favorables al sitio mayor de unión (ARM2-ARM4) de las importinas α humanas la cual es una región importante de unión a proteínas virales.

Métricas

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