Nature Communications (Nov 2023)

Defining neutralization and allostery by antibodies against COVID-19 variants

  • 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

DOI
https://doi.org/10.1038/s41467-023-42408-x
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 23

Abstract

Read online

Abstract 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.