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Cell Death Dis
. 2024 Jun 28;15(6):458.
doi: 10.1038/s41419-024-06802-7. A broad neutralizing nanobody against SARS-CoV-2 engineered from an approved drug
Qianyun Liu # 1 , Yuchi Lu # 2 3 4 , Chenguang Cai # 5 , Yanyan Huang # 5 , Li Zhou 6 7 , Yanbin Guan 5 , Shiying Fu 5 , Youyou Lin 5 , Huan Yan 6 , Zhen Zhang 7 , Xiang Li 5 , Xiuna Yang 2 4 , Haitao Yang 2 4 , Hangtian Guo 8 , Ke Lan 9 10 , Yu Chen 11 12 , Shin-Chen Hou 13 , Yi Xiong 14 15 16
Affiliations
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 S351, S470-471and S493-494 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.
. 2024 Jun 28;15(6):458.
doi: 10.1038/s41419-024-06802-7. A broad neutralizing nanobody against SARS-CoV-2 engineered from an approved drug
Qianyun Liu # 1 , Yuchi Lu # 2 3 4 , Chenguang Cai # 5 , Yanyan Huang # 5 , Li Zhou 6 7 , Yanbin Guan 5 , Shiying Fu 5 , Youyou Lin 5 , Huan Yan 6 , Zhen Zhang 7 , Xiang Li 5 , Xiuna Yang 2 4 , Haitao Yang 2 4 , Hangtian Guo 8 , Ke Lan 9 10 , Yu Chen 11 12 , Shin-Chen Hou 13 , Yi Xiong 14 15 16
Affiliations
- PMID: 38937437
- DOI: 10.1038/s41419-024-06802-7
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 S351, S470-471and S493-494 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.