Defining neutralization and allostery by antibodies against COVID-19 variants

Defining neutralization and allostery by antibodies against COVID-19 variants

Nature Communications

10.1038/s41467-023-42408-x

http://dx.doi.org/10.1038/s41467-023-42408-x

Nikhil Kumar Tulsian, Raghuvamsi Venkata Palur, Xinlei Qian, Yue Gu, Bhuvaneshwari D/O Shunmuganathan, Firdaus Samsudin, Yee Hwa Wong, Jianqing Lin, Kiren Purushotorman, Mary McQueen Kozma, Bei Wang, Julien Lescar, Cheng-I Wang, Ravindra Kumar Gupta, Peter John Bond, Paul Anthony MacAry

01 November 2023

Tulsian, N. K., Palur, R. V., Qian, X., Gu, Y., D/O Shunmuganathan, B., Samsudin, F., Wong, Y. H., Lin, J., Purushotorman, K., Kozma, M. M., Wang, B., Lescar, J., Wang, C.-I., Gupta, R. K., Bond, P. J., & MacAry, P. A. (2023). Defining neutralization and allostery by antibodies against COVID-19 variants. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-42408-x

AbstractThe 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.

Attribution 4.0 International (CC BY 4.0)

This research / project is supported by the A*STAR - AME Young Investigator Research Grant (YIRG)
Grant Reference no. : A2084c0159

This research / project is supported by the A*STAR - ID HTPO Seed Fund
Grant Reference no. : C211418001

This research / project is supported by the National Medical Research Council - COVID-19 SARS-CoV-2 antibody initiative
Grant Reference no. : R-571-000-081-213

This research / project is supported by the National Medical Research Council - SCOPE Fund
Grant Reference no. : R-711-000-058-598

This research is supported by core funding from: BII A*STAR
Grant Reference no. :

https://oar.a-star.edu.sg/communities-collections/articles/19970

2041-1723

Bioinformatics Institute