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Arquitectura molecular del virus SARS-CoV-2
Hangping Yao1, Yutong Song2, Yong Chen2
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China; National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
Cell
|September 27, 2020
Resumen
Los investigadores visualizaron la estructura completa del virus SARS-CoV-2, revelando la conformación nativa de las proteínas de punta y las ribonucleoproteínas internas. Esta arquitectura detallada explica cómo el virus empaqueta eficientemente su material genético.
Área de la Ciencia:
- Virología
- Biología estructural
- Microscopía criolectrónica
Sus antecedentes:
- La pandemia de COVID-19 es causada por el virus SARS-CoV-2.
- Comprender la arquitectura viral completa es crucial para desarrollar terapias efectivas.
- Los estudios anteriores se centraron en proteínas individuales, dejando la estructura del virus intacta en gran medida desconocida.
Objetivo del estudio:
- Para determinar el ensamblaje molecular de alta resolución del auténtico virus SARS-CoV-2.
- Para aclarar las estructuras nativas de los componentes virales clave, incluidas las proteínas de pico y las ribonucleoproteínas.
- Para entender el mecanismo de envasado de ARN viral.
Principales métodos:
- Se utilizó la criotomografía electrónica (Cryo-ET) para obtener imágenes de virus intactos.
- Se utilizó el promedio del subtomograma (STA) para reconstruir estructuras de alta resolución.
- La espectrometría de masas analizó las composiciones de glicanos ligados a N en proteínas nativas de picos.
Principales resultados:
- Las estructuras nativas de las proteínas de pico (S) del SARS-CoV-2 en los estados previos y posteriores a la fusión se resolvieron a 8,7-11 Å.
- Los estados de procesamiento de glicanos ligados a N en picos nativos fueron similares a las glicoproteínas recombinantes.
- Se reveló la conformación nativa y el ensamblaje de orden superior de las ribonucleoproteínas (RNP).
- Se caracterizó la arquitectura detallada del virus, incluido el empaquetado de ARN dentro de la luz.
Conclusiones:
- El estudio proporciona detalles sin precedentes sobre la arquitectura viral del SARS-CoV-2.
- Los conocimientos estructurales sobre las proteínas del pico y las RNP avanzan en nuestra comprensión del ensamblaje viral y la infección.
- Los hallazgos ofrecen una base para diseñar estrategias antivirales específicas.
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