TY - JOUR T1 - Potent SARS-CoV-2 Neutralizing Antibodies Directed Against Spike N-Terminal Domain Target a Single Supersite JF - bioRxiv DO - 10.1101/2021.01.10.426120 SP - 2021.01.10.426120 AU - Gabriele Cerutti AU - Yicheng Guo AU - Tongqing Zhou AU - Jason Gorman AU - Myungjin Lee AU - Micah Rapp AU - Eswar R. Reddem AU - Jian Yu AU - Fabiana Bahna AU - Jude Bimela AU - Yaoxing Huang AU - Phinikoula S. Katsamba AU - Lihong Liu AU - Manoj S. Nair AU - Reda Rawi AU - Adam S. Olia AU - Pengfei Wang AU - Gwo-Yu Chuang AU - David D. Ho AU - Zizhang Sheng AU - Peter D. Kwong AU - Lawrence Shapiro Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/01/11/2021.01.10.426120.abstract N2 - 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. ER -