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Updated: Jan 29, 2026

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Cribado de péptidos para unirse e inhibir funcionalmente el péptido de fusión de SARS-CoV-2 mediante la visualización

Ajay Pal^1,2, Neeladri Sekhar Roy³, Matthew Angeliadis^1,4

¹School of Medicine, University College Dublin, D04 C1P1 Dublin, Ireland.

Molecules (Basel, Switzerland)

|January 28, 2026

Resumen

Los investigadores exploraron péptidos para inhibir los coronavirus dirigiéndose al péptido de fusión de espiga (FP). Si bien las pantallas iniciales de péptidos no lograron inhibir la infección por SARS-CoV-2, proporcionaron información para el desarrollo de futuros disruptores de FP pancoronavíricos.

Área de la Ciencia:

Virología
Bioquímica
Descubrimiento de fármacos

Sus antecedentes:

El péptido de fusión de espiga (FP) conservado de los coronavirus presenta un objetivo potencial para terapias antivirales de amplio espectro.
El desarrollo de inhibidores pancoronavíricos requiere la identificación de moléculas que puedan interrumpir mecanismos virales conservados.

Objetivo del estudio:

Identificar nuevos inhibidores peptídicos dirigidos al péptido de fusión de espiga de SARS-CoV-2 conservado (FP).
Explorar bibliotecas de visualización de fagos para descubrir péptidos con potencial actividad inhibidora pancoronavírica.

Principales métodos:

Cribado de una biblioteca aleatoria de péptidos de 7 pb (NEB PhD-7 pb) contra el FP de SARS-CoV-2.
Síntesis de péptidos identificados como D-péptidos resistentes a proteólisis.
Cribado de una biblioteca de visualización de fagos derivada de proteomas de regiones desordenadas humanas.
Modelado estructural de dinámica molecular para dilucidar las interacciones de unión.

Principales resultados:

Diez D-péptidos de la biblioteca aleatoria no mostraron inhibición de la infección por SARS-CoV-2 en cultivos celulares.
Dos péptidos superpuestos de 14 pb de OTUD1 se identificaron a partir de la biblioteca proteómica.
Un péptido sintético basado en secuencias de OTUD1 no inhibió significativamente la entrada viral.
El modelado molecular reveló un modo de unión estable entre un péptido de OTUD1 y el FP, lo que sugiere potencial para el futuro diseño de inhibidores.

Conclusiones:

Las estrategias de visualización de fagos, aunque no produjeron inhibidores directos, facilitaron el desarrollo de un modelo computacional para disruptores de FP.
El estudio proporciona una base para el diseño de futuros inhibidores de FP pancoronavíricos basados en información estructural.

Palabras clave:

OTUD1 SARS-CoV-2 inhibidores de SARS-CoV-2 visualización de fagos peptídicos combinatorios péptido de fusión visualización de fagos peptídicos de proteómica péptidos retro-inverso

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