A Noncompeting Pair of Human Neutralizing Antibodies Block COVID-19 Virus Binding to Its Receptor ACE2

Overview

Journal Science

Specialty Science

Date 2020 May 15

PMID 32404477

Citations 674

Authors

Yan Wu

Feiran Wang

Chenguang Shen

Weiyu Peng

Delin Li

Cheng Zhao

Zhaohui Li

Shihua Li

Yuhai Bi

Yang Yang

Yuhuan Gong

Haixia Xiao

Zheng Fan

Shuguang Tan

Guizhen Wu

Wenjie Tan

Xuancheng Lu

Changfa Fan

Qihui Wang

Yingxia Liu

Chen Zhang

Jianxun Qi

George Fu Gao

Feng Gao

Lei Liu

Affiliations

Soon will be listed here.

Abstract

Neutralizing antibodies could potentially be used as antivirals against the coronavirus disease 2019 (COVID-19) pandemic. Here, we report isolation of four human-origin monoclonal antibodies from a convalescent patient, all of which display neutralization abilities. The antibodies B38 and H4 block binding between the spike glycoprotein receptor binding domain (RBD) of the virus and the cellular receptor angiotensin-converting enzyme 2 (ACE2). A competition assay indicated different epitopes on the RBD for these two antibodies, making them a potentially promising virus-targeting monoclonal antibody pair for avoiding immune escape in future clinical applications. Moreover, a therapeutic study in a mouse model validated that these antibodies can reduce virus titers in infected lungs. The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide a structural basis for rational vaccine design.

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