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A human antibody with blocking activity to RBD proteins of multiple SARS-CoV-2 variants including B.1.351 showed potent prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus macaques

By Su-Jun Deng, Xiaodan cao, Chunyin Gu, Zongda Wang, Peipei Liu, Xiaowu Liu, Li Gao, Fangfang Jia, Li Yu, Nan Li, Guoping Jiang, Jianjian Zhang, Lu Yang, Meng Shi, Tianquan Hou, Yanan Li, Weichen Liang, Guoqiao Lu, Congyi Yang, Yuting Wang, Kaiwen Xia, Zheng Xiao, Jianhua Xue, Xueyi Huang, Xin Chen, Zhongzong Pan, Xueping Wang, Haibing Guo, Hong Liang, Yanfeng Yao, Ge Gao, Yun Peng, Xue Hu, Juan Min, Yiwu Zhou, Kunpeng Liu, Weiwei Guo, Zhiming Yuan, Donglin Song, Wuxiang Guan, Haixia Ma, Xiao Hu, Yecheng Zhang, Zhen Chen, Chao Shan

Posted 07 Feb 2021
bioRxiv DOI: 10.1101/2021.02.07.429299

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein for infection. After the virus sequence was published, we identified two potent antibodies against SARS-CoV-2 RBD from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a phase I clinical trial, showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS- CoV-2 variants and result in more efficient control of the COVID-19 pandemic.

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