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La senescencia inducida por el virus es un conductor y un objetivo terapéutico en el COVID-19

Soyoung Lee^1,2,3, Yong Yu⁴, Jakob Trimpert⁵

¹Medical Department of Hematology, Oncology and Tumor Immunology, Molekulares Krebsforschungszentrum (MKFZ), Charité - Universitätsmedizin, Berlin, Germany.

|September 13, 2021

Resumen

La infección por SARS-CoV-2 desencadena la senescencia inducida por el virus (VIS), una respuesta al estrés celular. Los senolíticos dirigidos a las células VIS redujeron la enfermedad pulmonar y la inflamación similares a la COVID-19 en modelos animales, lo que sugiere una nueva estrategia de tratamiento.

Área de la Ciencia:

Virología
Inmunología
Biología celular

Sus antecedentes:

La gravedad del COVID-19 está relacionada con respuestas inmunológicas desreguladas y daño a los órganos.
La senescencia celular, una respuesta al estrés, ha sido implicada en el envejecimiento y las enfermedades.

Objetivo del estudio:

Para investigar si la infección por SARS-CoV-2 induce la senescencia celular.
Para explorar el papel de la senescencia inducida por virus (VIS) en la patogénesis de COVID-19.
Evaluar los senolíticos como una estrategia terapéutica potencial para el COVID-19.

Principales métodos:

Se evaluaron los marcadores de senescencia celular en las células infectadas por SARS-CoV-2 y las muestras de pacientes con COVID-19.
Investigó el fenotipo secretor asociado a la senescencia (SASP) in vitro.
Se utilizaron fármacos senolíticos (navitoclax, dasatinib más quercetina) en modelos animales infectados por el SARS-CoV-2 (hámsters, ratones).

Principales resultados:

La infección por SARS-CoV-2 indujo la senescencia celular (VIS) con un SASP proinflamatorio.
Los pacientes con COVID-19 mostraron un aumento de los marcadores de senescencia y los factores SASP.
El VIS contribuyó al daño endotelial, la trombosis y la inflamación, imitando la patología del COVID-19.
El tratamiento senolítico eliminó las células VIS, redujo la enfermedad pulmonar y mitigó la inflamación en los animales infectados.

Conclusiones:

La senescencia inducida por el virus (VIS) es un mecanismo patogénico clave en COVID-19, que impulsa la escalada de citoquinas y el daño a los órganos.
El tratamiento del VIS con senolíticos representa una vía terapéutica prometedora para el COVID-19 y potencialmente para otras infecciones virales.

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