RT Journal Article
SR Electronic
T1 Potent SARS-CoV-2 Neutralizing Antibodies Directed Against Spike N-Terminal Domain Target a Single Supersite
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.10.426120
DO 10.1101/2021.01.10.426120
A1 Gabriele Cerutti
A1 Yicheng Guo
A1 Tongqing Zhou
A1 Jason Gorman
A1 Myungjin Lee
A1 Micah Rapp
A1 Eswar R. Reddem
A1 Jian Yu
A1 Fabiana Bahna
A1 Jude Bimela
A1 Yaoxing Huang
A1 Phinikoula S. Katsamba
A1 Lihong Liu
A1 Manoj S. Nair
A1 Reda Rawi
A1 Adam S. Olia
A1 Pengfei Wang
A1 Gwo-Yu Chuang
A1 David D. Ho
A1 Zizhang Sheng
A1 Peter D. Kwong
A1 Lawrence Shapiro
YR 2021
UL http://biorxiv.org/content/early/2021/01/11/2021.01.10.426120.abstract
AB Numerous antibodies that neutralize SARS-CoV-2 have been identified, and these generally target either the receptor-binding domain (RBD) or the N-terminal domain (NTD) of the viral spike. While RBD-directed antibodies have been extensively studied, far less is known about NTD-directed antibodies. Here we report cryo-EM and crystal structures for seven potent NTD-directed neutralizing antibodies in complex with spike or isolated NTD. These structures defined several antibody classes, with at least one observed in multiple convalescent donors. The structures revealed all seven antibodies to target a common surface, bordered by glycans N17, N74, N122, and N149. This site – formed primarily by a mobile β-hairpin and several flexible loops – was highly electropositive, located at the periphery of the spike, and the largest glycan-free surface of NTD facing away from the viral membrane. Thus, in contrast to neutralizing RBD-directed antibodies that recognize multiple non-overlapping epitopes, potent NTD-directed neutralizing antibodies target a single supersite.Competing Interest StatementDDH, YH, JY, LL, MSN and PW are inventors of a patent describing some of the antibodies reported on here.