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Broad neutralizing nanobody against SARS-CoV-2 engineered from pre-designed synthetic library
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; Yu Chen; Xiang Li; Shin-Chen Hou; Yi Xiong.
Affiliation
  • Qianyun Liu; State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei, China
  • Chenguang Cai; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Yanyan Huang; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Li Zhou; State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei, China
  • Yanbin Guan; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Shiying Fu; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Youyou Lin; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Ting Yang; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Xiaohua Liang; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Nanyan Wang; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Fengzhi Zhang; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Qi Sun; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Ying Bai; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Yu Chen; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Huan Yan; Wuhan University
  • Zhen Zhang; State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei, China
  • Ke Lan; State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei, China
  • Yu Chen; State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei, China
  • Xiang Li; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Shin-Chen Hou; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
  • Yi Xiong; Bioduro-sundia LLC., Wuxi 214174, Jiangsu, China.
Preprint in English | bioRxiv | ID: ppbiorxiv-455523
ABSTRACT
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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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental_studies Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental_studies Language: English Year: 2021 Document type: Preprint
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