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Bolsa de unión de ácidos grasos libres en la estructura cerrada de la proteína del pico del SARS-CoV-2

Christine Toelzer^1,2, Kapil Gupta^1,2, Sathish K N Yadav^1,2

¹School of Biochemistry, University of Bristol, 1 Tankard's Close, Bristol BS8 1TD, UK.

Science (New York, N.Y.)

|September 22, 2020

Resumen

El ácido linoleico (LA) se une a la proteína del pico del SARS-CoV-2, estabilizando su estructura y reduciendo la interacción con el ACE2. Este descubrimiento puede conducir a nuevas estrategias terapéuticas contra el COVID-19.

Área de la Ciencia:

Biología estructural
Virología
La bioquímica

Sus antecedentes:

La enfermedad por coronavirus 2019 (COVID-19), causada por el SARS-CoV-2, es una crisis de salud mundial.
Comprender los mecanismos del SARS-CoV-2 es crucial para desarrollar terapias efectivas.
La glicoproteína del pico (S) impulsa la infectividad viral y la patología.

Objetivo del estudio:

Para aclarar la base estructural de la infectividad del SARS-CoV-2.
Investigar el papel de los ácidos grasos libres en la función de la glicoproteína S.
Para identificar posibles objetivos terapéuticos para el COVID-19.

Principales métodos:

Microscopía cryoelectrónica con una resolución de 2,85 angstroms.
Análisis estructural de la glicoproteína S del SARS-CoV-2.
Ensayos in vitro para evaluar la interacción ACE2 y la replicación viral.
Suplementación de ácido linoleico en las células humanas.

Principales resultados:

La glicoproteína S del SARS-CoV-2 tiene tres bolsas de unión para el ácido linoleico (LA).
La unión de LA estabiliza la glicoproteína S en una conformación "bloqueada".
Esta conformación reduce la interacción con la enzima convertidora de angiotensina 2 (ACE2) in vitro.
LA sinergiza con el remdesivir para suprimir la replicación del SARS-CoV-2 en las células humanas.
Se sugieren bolsas de unión de LA similares en el SARS-CoV y el MERS-CoV.

Conclusiones:

El ácido linoleico interactúa directamente con la proteína del pico del SARS-CoV-2.
La unión de LA representa un nuevo mecanismo que influye en la entrada y estabilidad del virus.
Dirigirse a la unión de LA ofrece una estrategia terapéutica potencial para el COVID-19 y los coronavirus relacionados.

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