Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529

The rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (Omicron) variant and its resistance to neutralization by vaccinee and convalescent sera are driving a search for monoclonal antibodies with potent neutralization. To provide insight into effective neutral...

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Detalles Bibliográficos
Autores principales: Zhou, Tongqing, Wang, Lingshu, Misasi, John, Pegu, Amarendra, Zhang, Yi, Harris, Darcy R., Olia, Adam S., Talana, Chloe Adrienna, Yang, Eun Sung, Chen, Man, Choe, Misook, Shi, Wei, Teng, I-Ting, Creanga, Adrian, Jenkins, Claudia, Leung, Kwanyee, Liu, Tracy, Stancofski, Erik-Stephane D., Stephens, Tyler, Zhang, Baoshan, Tsybovsky, Yaroslav, Graham, Barney S., Mascola, John R., Sullivan, Nancy J., Kwong, Peter D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580340/
https://www.ncbi.nlm.nih.gov/pubmed/35324257
http://dx.doi.org/10.1126/science.abn8897
Descripción
Sumario:The rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (Omicron) variant and its resistance to neutralization by vaccinee and convalescent sera are driving a search for monoclonal antibodies with potent neutralization. To provide insight into effective neutralization, we determined cryo–electron microscopy structures and evaluated receptor binding domain (RBD) antibodies for their ability to bind and neutralize B.1.1.529. Mutations altered 16% of the B.1.1.529 RBD surface, clustered on an RBD ridge overlapping the angiotensin-converting enzyme 2 (ACE2)–binding surface and reduced binding of most antibodies. Substantial inhibitory activity was retained by select monoclonal antibodies—including A23-58.1, B1-182.1, COV2-2196, S2E12, A19-46.1, S309, and LY-CoV1404—that accommodated these changes and neutralized B.1.1.529. We identified combinations of antibodies with synergistic neutralization. The analysis revealed structural mechanisms for maintenance of potent neutralization against emerging variants.

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