Structural and energetic profiling of SARS-CoV-2 receptor binding domain antibody recognition and the impact of circulating variants

The SARS-CoV-2 pandemic highlights the need for a detailed molecular understanding of protective antibody responses. This is underscored by the emergence and spread of SARS-CoV-2 variants, including Alpha (B.1.1.7) and Delta (B.1.617.2), some of which appear to be less effectively targeted by curren...

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Bibliographic Details
Published in:PLoS computational biology 2021-09, Vol.17 (9), p.e1009380-e1009380
Main Authors: Yin, Rui, Guest, Johnathan D, Taherzadeh, Ghazaleh, Gowthaman, Ragul, Mittra, Ipsa, Quackenbush, Jane, Pierce, Brian G
Format: Article
Language:English
Subjects:
Antibodies
Antigen-antibody reactions
Antigenic determinants
Binding
Binding sites
Biology and Life Sciences
Clustering
Computer applications
Domains
Epitopes
Genes
Glycoproteins
Medicine and Health Sciences
Monoclonal antibodies
Mutation
Pandemics
Physical Sciences
Physiological aspects
Principal components analysis
Receptors
Recognition
Research and Analysis Methods
Residues
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Structural analysis
Structure
Vaccines
Viral antibodies
Viral diseases
Viral proteins
Virus research
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Summary:The SARS-CoV-2 pandemic highlights the need for a detailed molecular understanding of protective antibody responses. This is underscored by the emergence and spread of SARS-CoV-2 variants, including Alpha (B.1.1.7) and Delta (B.1.617.2), some of which appear to be less effectively targeted by current monoclonal antibodies and vaccines. Here we report a high resolution and comprehensive map of antibody recognition of the SARS-CoV-2 spike receptor binding domain (RBD), which is the target of most neutralizing antibodies, using computational structural analysis. With a dataset of nonredundant experimentally determined antibody-RBD structures, we classified antibodies by RBD residue binding determinants using unsupervised clustering. We also identified the energetic and conservation features of epitope residues and assessed the capacity of viral variant mutations to disrupt antibody recognition, revealing sets of antibodies predicted to effectively target recently described viral variants. This detailed structure-based reference of antibody RBD recognition signatures can inform therapeutic and vaccine design strategies.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1009380