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Dinámica estructural de las UTR del virus del dengue y su ciclización
Zachary E Robinson1, Higor Sette Pereira1, Michael H D'Souza1
1Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute, University of Lethbridge, 4401 University Drive, Lethbridge, AB, T1K 3M4, Canada.
Biophysical journal
|September 7, 2025
Resumen
Se estudiaron las estructuras de ARN del virus del dengue (DENV) para comprender la replicación. Los investigadores revelaron conformaciones flexibles de ARN cruciales para la ciclización de DENV, que ofrecen nuevos objetivos farmacológicos.
Área de la Ciencia:
- Virología
- Biología estructural
- Biología molecular
Sus antecedentes:
- El virus del dengue (DENV) causa problemas de salud globales significativos, con alrededor de 400 millones de infecciones al año.
- La replicación de DENV se basa en las interacciones ARN-ARN mediadas por regiones no traducidas (UTR).
- La comprensión de la estructura de DENV UTR es clave para inhibir la replicación viral.
Objetivo del estudio:
- Investigar la organización estructural y las propiedades de unión de las UTR 5' y 3' de DENV.
- Para aclarar la flexibilidad conformacional de las UTR de DENV durante la replicación.
- Proporcionar información para el desarrollo de terapias antivirales dirigidas.
Principales métodos:
- Purificación in vitro de las UTR 5' y 3' de DENV.
- Técnicas biofísicas, incluida la dispersión de rayos X en ángulo pequeño (SAXS).
- Métodos computacionales para el análisis estructural y vinculante.
Principales resultados:
- Las UTR DENV 5' y 3' se unen con una alta afinidad (40 nM) en una estequiometría 1:1.
- SAXS proporcionó la primera caracterización estructural de DENV UTR, revelando múltiples conformaciones.
- Se identificaron las características clave de la adaptabilidad estructural y el plegamiento dinámico.
Conclusiones:
- El estudio mejora la comprensión de los mecanismos de ciclización de DENV.
- Las conformaciones de ARN flexibles son críticas para la replicación de DENV.
- Los hallazgos allanan el camino para nuevas estrategias terapéuticas dirigidas a las estructuras de ARN viral.
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