Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class
Micah Rapp, Yicheng Guo, Eswar R. Reddem, Jian Yu, Lihong Liu, Pengfei Wang, Gabriele Cerutti, Phinikoula S. Katsamba, Jude Bimela, Fabiana Bahna, Seetha Mannepalli, Baoshan Zhang, Peter D. Kwong, Yaoxing Huang, David D. Ho, Lawrence Shapiro, Zizhang Sheng
Abstract
. Despite these similarities, class members bind both RBD-up and -down conformations of the spike, with a subset of antibodies using elongated CDRH3s to recognize glycan N343 on a neighboring RBD-a quaternary interaction accommodated by an increase in RBD separation of up to 12 Å. The VH1-2 antibody class, thus, uses modular recognition encoded by modular genetic elements to effect potent neutralization, with the VH-gene component specifying recognition of RBD and the CDRH3 component specifying quaternary interactions.