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Ibrutinib inhibe la replicación de múltiples virus de la viruela al dirigirse a la tirosina quinasa de Bruton

Kang Niu¹, Xiru Wang¹, Qiwei Jiang²

¹National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.

Journal of virology

|August 20, 2025

Resumen

Ibrutinib combate eficazmente el mpox y otros poxvirus inhibiendo la replicación viral. Este inhibidor de la tirosina quinasa de Bruton (BTK) es prometedor como agente antiviral de amplio espectro contra las amenazas zoonóticas emergentes.

Área de la Ciencia:

Virología
Descubrimiento de drogas
Inmunología

Sus antecedentes:

Los brotes mundiales de viruela del mono (mpox) subrayan la necesidad urgente de terapias antivirales eficaces contra el ortopoxvirus.
Los tratamientos existentes para las infecciones por virus de la viruela son limitados, especialmente para enfermedades como la enfermedad de la piel nodular (LSD) que afecta al ganado.
El cribado de alto rendimiento identificó ibrutinib, un inhibidor de la tirosina quinasa de Bruton (BTK), como un agente antiviral potencial contra el virus de la vacuna (VACV).

Objetivo del estudio:

Evaluar la eficacia antiviral de ibrutinib contra múltiples virus de la varicela, incluidos el virus de la varicela (MPXV), el VACV y el virus de la enfermedad nodular de la piel (LSDV).
Investigar el mecanismo de acción de la actividad antiviral de ibrutinib.
Para determinar el papel de la tirosina quinasa de Bruton (BTK) en la replicación del virus de la viruela.

Principales métodos:

Se realizaron ensayos antivirales in vitro en múltiples líneas celulares para evaluar el efecto de ibrutinib en la replicación de VACV, MPXV y LSDV.
En los estudios in vivo se utilizaron ratones BALB/ c infectados por VACV para evaluar el potencial terapéutico de ibrutinib, monitoreando la supervivencia, el peso, las lesiones y la carga viral.
Los estudios mecanicistas examinaron el impacto de ibrutinib en la síntesis de proteínas virales y la replicación del ADN, junto con la manipulación de BTK (nockdown y sobreexpresión).

Principales resultados:

Ibrutinib demostró una inhibición significativa de la replicación de VACV, MPXV y LSDV in vitro.
In vivo, el tratamiento con ibrutinib mejoró las tasas de supervivencia, redujo la gravedad de la enfermedad y redujo la carga viral en ratones infectados con VACV.
El mecanismo de Ibrutinib implica la inhibición de la síntesis de proteínas virales y la replicación del ADN; BTK fue identificado como un factor anfitrión pro-viral.

Conclusiones:

Ibrutinib es un potente agente antiviral eficaz contra una variedad de poxvirus, incluidos el MPXV y el LSDV.
El estudio identifica a BTK como un factor huésped crítico que apoya la replicación del virus de la viruela, lo que lo convierte en un objetivo terapéutico viable.
Ibrutinib representa un candidato prometedor para el desarrollo de terapias antivirales de amplio espectro contra las infecciones por poxvirus emergentes y reemergentes.

Palabras clave:

BTK (en inglés)El uso de ibrutinib Acción antiviral Virus de la enfermedad nodular de la piel El virus de la mpox

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