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Cooperatividad y comunicación entre los sitios activos de la proteasa principal del SARS-CoV-2 dimérica

Sarah N Zvornicanin¹, Ala M Shaqra¹, Julia Flynn¹

¹Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.

Science advances

|January 16, 2026

Resumen

La proteasa principal (Mpro) del coronavirus funciona como un dímero. Este estudio revela que la heterodimerización mejora la Mpro

Área de la Ciencia:

Bioquímica
Biología Estructural
Virología

Sus antecedentes:

La proteasa principal (Mpro) del coronavirus es un objetivo farmacológico clave para el SARS-CoV-2.
La Mpro del SARS-CoV-2 funciona como un dímero, exhibiendo actividad catalítica cooperativa.
Los mecanismos de comunicación entre los dos sitios activos en la Mpro del SARS-CoV-2 siguen sin estar claros.

Objetivo del estudio:

Investigar la interacción entre la cooperatividad, la dimerización y la escisión del sustrato en la Mpro del SARS-CoV-2.
Elucidar las vías de comunicación y la significancia funcional de la arquitectura dimérica.

Principales métodos:

Ensayos enzimáticos utilizando heterodímeros de monómeros de Mpro activos e inactivos.
Cristalografía de rayos X para obtener información estructural.
Caracterización de proteínas y mutagénesis dirigida para sondear redes de residuos.

Principales resultados:

La heterodimerización de la Mpro del SARS-CoV-2 aumentó significativamente la eficiencia de escisión por monómero activo.
Se identificó una red de residuos críticos que unen los dos sitios activos.
Los estudios de mutagénesis confirmaron el papel de estos residuos en la comunicación intersitio.

Conclusiones:

La estructura dimérica de la Mpro del SARS-CoV-2 es crucial para su función catalítica mejorada.
La comunicación intersitio, mediada por residuos específicos, modula la actividad de la Mpro.
La comprensión de estos mecanismos proporciona información sobre el ciclo de reacción de la Mpro y las estrategias terapéuticas potenciales.

Palabras clave:

proteasa principal del SARS-CoV-2 cooperatividad sitio activo dimerización inhibidores de proteasa

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