RT Journal Article
SR Electronic
T1 Potent Neutralizing Antibodies Directed to Multiple Epitopes on SARS-CoV-2 Spike
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.17.153486
DO 10.1101/2020.06.17.153486
A1 Lihong Liu
A1 Pengfei Wang
A1 Manoj S. Nair
A1 Jian Yu
A1 Micah Rapp
A1 Qian Wang
A1 Yang Luo
A1 Jasper F-W. Chan
A1 Vincent Sahi
A1 Amir Figueroa
A1 Xinzheng V. Guo
A1 Gabriele Cerutti
A1 Jude Bimela
A1 Jason Gorman
A1 Tongqing Zhou
A1 Zhiwei Chen
A1 Kwok-Yung Yuen
A1 Peter D. Kwong
A1 Joseph G. Sodroski
A1 Michael T. Yin
A1 Zizhang Sheng
A1 Yaoxing Huang
A1 Lawrence Shapiro
A1 David D. Ho
YR 2020
UL http://biorxiv.org/content/early/2020/07/16/2020.06.17.153486.abstract
AB The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that are overlapping with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of the closed, “all RBD-down” conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.Competing Interest StatementA provisional patent application has been filed for the monoclonal antibodies described in the manuscript. L.L. and D.D.H. are inventors.