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Broad neutralizing nanobody against SARS-CoV-2 engineered from pre-designed synthetic library

By Qianyun Liu, Chenguang Cai, Yanyan Huang, Li Zhou, Yanbin Guan, Shiying Fu, Youyou Lin, Ting Yang, Xiaohua Liang, Nanyan Wang, Fengzhi Zhang, Qi Sun, Ying Bai, Yu Chen, Huan Yan, Zhen Zhang, Ke Lan, Xiang Li, Shin-Chen Hou, Yi Xiong

Posted 09 Aug 2021
bioRxiv DOI: 10.1101/2021.08.07.455523

SARS-CoV-2 infection is initiated with Spike glycoprotein binding to the receptor of human angiotensin converting enzyme 2 via its receptor binding domain. Blocking this interaction is considered as an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody, VHH60, directly produced from a humanized synthetic nanobody library. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein with a KD of 2.56 nM, inhibits infections of both live SARS-CoV-2 and pseudotyped viruses harboring wildtype, escape mutations and prevailing variants at nanomolar level. VHH60 also suppresses SARS-CoV-2 infection and propagation 50-fold better and protects mice from death two times longer than that of control group after live virus inoculation on mice. VHH60 therefore is a powerful synthetic nanobody with a promising profile for disease control against COVID19.

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