tetano
Editor, Senior Moderator
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[SUP] #[/SUP][SUP] 1 [/SUP], Yuchi Lu[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Chenguang Cai[SUP] #[/SUP][SUP] 5 [/SUP], Yanyan Huang[SUP] #[/SUP][SUP] 5 [/SUP], Li Zhou[SUP] 6 7 [/SUP], Yanbin Guan[SUP] 5 [/SUP], Shiying Fu[SUP] 5 [/SUP], Youyou Lin[SUP] 5 [/SUP], Huan Yan[SUP] 6 [/SUP], Zhen Zhang[SUP] 7 [/SUP], Xiang Li[SUP] 5 [/SUP], Xiuna Yang[SUP] 2 4 [/SUP], Haitao Yang[SUP] 2 4 [/SUP], Hangtian Guo[SUP] 8 [/SUP], Ke Lan[SUP] 9 10 [/SUP], Yu Chen[SUP] 11 12 [/SUP], Shin-Chen Hou[SUP] 13 [/SUP], Yi Xiong[SUP] 14 15 16 [/SUP]
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 S[SUP]351[/SUP], S[SUP]470-471[/SUP]and S[SUP]493-494[/SUP] 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[SUP] #[/SUP][SUP] 1 [/SUP], Yuchi Lu[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Chenguang Cai[SUP] #[/SUP][SUP] 5 [/SUP], Yanyan Huang[SUP] #[/SUP][SUP] 5 [/SUP], Li Zhou[SUP] 6 7 [/SUP], Yanbin Guan[SUP] 5 [/SUP], Shiying Fu[SUP] 5 [/SUP], Youyou Lin[SUP] 5 [/SUP], Huan Yan[SUP] 6 [/SUP], Zhen Zhang[SUP] 7 [/SUP], Xiang Li[SUP] 5 [/SUP], Xiuna Yang[SUP] 2 4 [/SUP], Haitao Yang[SUP] 2 4 [/SUP], Hangtian Guo[SUP] 8 [/SUP], Ke Lan[SUP] 9 10 [/SUP], Yu Chen[SUP] 11 12 [/SUP], Shin-Chen Hou[SUP] 13 [/SUP], Yi Xiong[SUP] 14 15 16 [/SUP]
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 S[SUP]351[/SUP], S[SUP]470-471[/SUP]and S[SUP]493-494[/SUP] 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.