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Defining neutralization and allostery by antibodies against COVID-19 variants

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 antibod...

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Detalles Bibliográficos
Autores principales: Tulsian, Nikhil Kumar, Palur, Raghuvamsi Venkata, Qian, Xinlei, Gu, Yue, D/O Shunmuganathan, Bhuvaneshwari, Samsudin, Firdaus, Wong, Yee Hwa, Lin, Jianqing, Purushotorman, Kiren, Kozma, Mary McQueen, Wang, Bei, Lescar, Julien, Wang, Cheng-I, Gupta, Ravindra Kumar, Bond, Peter John, MacAry, Paul Anthony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618280/
https://www.ncbi.nlm.nih.gov/pubmed/37907459
http://dx.doi.org/10.1038/s41467-023-42408-x
Descripción
Sumario: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.