作者
John M Errico, Haiyan Zhao, Rita E Chen, Zhuoming Liu, James Brett Case, Meisheng Ma, Aaron J Schmitz, Michael J Rau, James AJ Fitzpatrick, Pei-Yong Shi, Michael S Diamond, Sean PJ Whelan, Ali H Ellebedy, Daved H Fremont
发表日期
2021/10/26
期刊
Cell Reports
卷号
37
期号
4
出版商
Elsevier
简介
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has necessitated the rapid development of antibody-based therapies and vaccines as countermeasures. Here, we use cryoelectron microscopy (cryo-EM) to characterize two protective anti-SARS-CoV-2 murine monoclonal antibodies (mAbs) in complex with the spike protein, revealing similarities between epitopes targeted by human and murine B cells. The more neutralizing mAb, 2B04, binds the receptor-binding motif (RBM) of the receptor-binding domain (RBD) and competes with angiotensin-converting enzyme 2 (ACE2). By contrast, 2H04 binds adjacent to the RBM and does not compete for ACE2 binding. Naturally occurring sequence variants of SARS-CoV-2 and corresponding neutralization escape variants selected in vitro map to our structurally defined epitopes, suggesting that SARS-CoV-2 might evade therapeutic antibodies …
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