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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Defining neutralization and allostery by antibodies against COVID-19 variants
Nature Communications, Volume 14, No. 1, Article 6967, Year 2023
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Description
The changing landscape of SARS-CoV-2 Spike protein is linked to the emergence of variants, immune-escape and reduced efficacy of the existing repertoire of anti-viral antibodies. The functional activity of neutralizing antibodies is linked to their quaternary changes occurring as a result of antibody-Spike trimer interactions. Here, we reveal the conformational dynamics and allosteric perturbations linked to binding of novel human antibodies and the viral Spike protein. We identified epitope hotspots, and associated changes in Spike dynamics that distinguish weak, moderate and strong neutralizing antibodies. We show the impact of mutations in Wuhan-Hu-1, Delta, and Omicron variants on differences in the antibody-induced conformational changes in Spike and illustrate how these render certain antibodies ineffective. Antibodies with similar binding affinities may induce destabilizing or stabilizing allosteric effects on Spike, with implications for neutralization efficacy. Our results provide mechanistic insights into the functional modes and synergistic behavior of human antibodies against COVID-19 and may assist in designing effective antiviral strategies. © 2023, The Author(s).
Authors & Co-Authors
Lescar, Julien
Singapore, Singapore City
Nanyang Technological University
Gupta, Ravindra K.
Singapore, Singapore City
National University of Singapore
United Kingdom, Cambridge
University of Cambridge
MacAry, Paul Anthony
Singapore, Singapore City
National University of Singapore
Statistics
Authors: 3
Affiliations: 4
Identifiers
Doi:
10.1038/s41467-023-42408-x
ISSN:
20411723
Research Areas
Covid