PT  - JOURNAL ARTICLE
AU  - Qianyun Liu
AU  - Chenguang Cai
AU  - Yanyan Huang
AU  - Li Zhou
AU  - Yanbin Guan
AU  - Shiying Fu
AU  - Youyou Lin
AU  - Ting Yang
AU  - Nanyan Wan
AU  - Fengzhi Zhang
AU  - Qi Sun
AU  - Ying Bai
AU  - Yu Chen
AU  - Xiaohua Liang
AU  - Huan Yan
AU  - Zhen Zhang
AU  - Ke Lan
AU  - Yu Chen
AU  - Xiang Li
AU  - Shin-Chen Hou
AU  - Yi Xiong
TI  - Broad neutralizing nanobody against SARS-CoV-2 engineered from pre-designed synthetic library
AID  - 10.1101/2021.08.07.455523
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.07.455523
4099  - http://biorxiv.org/content/early/2021/08/09/2021.08.07.455523.short
4100  - http://biorxiv.org/content/early/2021/08/09/2021.08.07.455523.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.