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Bases estructurales para una mayor infectividad y evasión inmune de las variantes del SARS-CoV-2
Yongfei Cai1,2, Jun Zhang1,2, Tianshu Xiao1,2
1Division of Molecular Medicine, Boston Children's Hospital, 3 Blackfan Street, Boston, MA 02115, USA.
Science (New York, N.Y.)
|June 25, 2021
Resumen
Las nuevas variantes del SARS-CoV-2, B.1.1.7 y B.1.351, muestran una mayor transmisibilidad y evasión inmune. El análisis estructural revela mutaciones clave en la proteína del pico que impulsa estas mejoras en la aptitud viral.
Área de la Ciencia:
- Virología
- Biología estructural
- Inmunología
Sus antecedentes:
- La aparición de las variantes de coronavirus 2 del síndrome respiratorio agudo severo de rápida propagación (SARS-CoV-2), como B.1.1.7 y B.1.351, ha impulsado la pandemia de COVID-19.
- Comprender las adaptaciones estructurales y funcionales de estas variantes es crucial para las estrategias de salud pública.
Objetivo del estudio:
- Determinar las estructuras de microscopía criolectrónica de los pinchos (S) de longitud completa para las variantes B.1.1.7 y B.1.351 del SARS-CoV-2.
- Para aclarar las propiedades bioquímicas y antigénicas de estos S trimers.
- Proporcionar conocimientos estructurales sobre la aptitud viral mejorada y los mecanismos de evasión inmune.
Principales métodos:
- Microscopía criolectrónica (crio-EM) para la determinación estructural de alta resolución de las cortadoras de espigas.
- Ensayos bioquímicos para evaluar las afinidades de unión y las propiedades funcionales.
- Perfiles antigénicos para evaluar la sensibilidad a la neutralización.
Principales resultados:
- Las sustituciones de aminoácidos en la proteína punta B.1.1.7 aumentan la accesibilidad y la afinidad del dominio de unión al receptor (RBD) para la enzima de conversión de la angiotensina 2 (ACE2), lo que sugiere una mayor transmisibilidad.
- La variante B.1.351 exhibe superficies antigénicas alteradas en los sitios neutralizantes clave de la proteína S, lo que confiere resistencia a los potentes anticuerpos neutralizantes.
- Los datos estructurales revelan cambios moleculares específicos que subyacen al aumento de la aptitud viral y el escape inmune.
Conclusiones:
- Las modificaciones estructurales de la variante B.1.1.7 mejoran su interacción con las células huésped, lo que podría explicar su rápida propagación.
- La variante B.1.351 demuestra capacidades de evasión inmunológica significativas debido a alteraciones en los sitios antigénicos de su proteína de pico.
- Estos hallazgos resaltan la evolución en curso del SARS-CoV-2 y la necesidad de un monitoreo continuo y la adaptación de las contramedidas.
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