Journal: Cell Death Dis / Year: 2024 Title: A broad neutralizing nanobody against SARS-CoV-2 engineered from an approved drug. Authors: Qianyun Liu / Yuchi Lu / Chenguang Cai / Yanyan Huang / Li Zhou / Yanbin Guan / Shiying Fu / Youyou Lin / Huan Yan / Zhen Zhang / Xiang Li / Xiuna Yang / Haitao Yang / Hangtian Guo / Ke Lan ...Authors: Qianyun Liu / Yuchi Lu / Chenguang Cai / Yanyan Huang / Li Zhou / Yanbin Guan / Shiying Fu / Youyou Lin / Huan Yan / Zhen Zhang / Xiang Li / Xiuna Yang / Haitao Yang / Hangtian Guo / Ke Lan / Yu Chen / Shin-Chen Hou / Yi Xiong / Abstract: SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven ...SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven to be an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody named VHH60, which was directly produced from an engineering nanobody library based on a commercialized nanobody within a very short period. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein at S, Sand S as determined by structural analysis, with an affinity of 2.56 nM. It inhibits infections of both ancestral SARS-CoV-2 strain and pseudotyped viruses harboring SARS-CoV-2 wildtype, key mutations or variants at the nanomolar level. Furthermore, VHH60 suppressed SARS-CoV-2 infection and propagation 50-fold better and protected mice from death for twice as long as the control group after SARS-CoV-2 nasal infections in vivo. Therefore, VHH60 is not only a powerful nanobody with a promising profile for disease control but also provides evidence for a highly effective and rapid approach to generating therapeutic nanobodies.
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