A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

Wu, Yan; Wang, Feiran; Shen, Chenguang; Peng, Weiyu; Li, Delin; Zhao, Cheng; Li, Zhaohui; Li, Shihua; Bi, Yuhai; Yang, Yang; Gong, Yuhuan; Xiao, Haixia; Fan, Zheng; Tan, Shuguang; Wu, Guizhen; Tan, Wenjie; Lu, Xuancheng; Fan, Changfa; Wang, Qihui; Liu, Yingxia; Zhang, Chen; Qi, Jianxun; Gao, George Fu; Gao, Feng; Liu, Lei

Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report isolation of four human-origin monoclonal antibodies from a convalescent patient, all of which display neutralization abilities. B38 and H4 block the binding between virus S-protein RBD and cellular receptor ACE2. A competition assay indicates their different epitopes on the RBD, making them a potential virus-targeting MAb-pair to avoid 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.