Double Lock of a Potent Human Monoclonal Antibody against SARS-CoV-2
Summary Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10-fold of effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the RBD, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19.Highlights <jats:list list-type="order">SARS-CoV-2 specific antibody, HB27, blocks viral receptor binding and membrane fusionHB27 confers prophylactic and therapeutic protection against SARS-CoV-2 in mice modelsRhesus macaques showed no adverse side effects when administered with HB27Cryo-EM studies suggest that HB27 sterically occludes SARS-CoV-2 from its receptor.
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Preprint| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
bioRxiv.org - (2020) vom: 28. Nov. Zur Gesamtaufnahme - year:2020 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhu, Ling [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2020.11.24.393629 |
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| funding: |
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| PPN (Katalog-ID): |
XBI019418906 |
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| 520 | |a Summary Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10-fold of effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the RBD, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19.Highlights <jats:list list-type="order">SARS-CoV-2 specific antibody, HB27, blocks viral receptor binding and membrane fusionHB27 confers prophylactic and therapeutic protection against SARS-CoV-2 in mice modelsRhesus macaques showed no adverse side effects when administered with HB27Cryo-EM studies suggest that HB27 sterically occludes SARS-CoV-2 from its receptor | ||
| 700 | 1 | |a Deng, Yong-Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Rong-Rong |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Chun-Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Chang-Fa |e verfasserin |4 aut | |
| 700 | 1 | |a Xing, Xiaorui |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Weijin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Na-Na |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Tian-Shu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Huiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Desheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Chunxia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yanjing |e verfasserin |4 aut | |
| 700 | 1 | |a Nie, Jianhui |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yao |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Shaw, Neil |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Qianqian |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiao-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Junjie |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Liangzhi |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Zihe |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Youchun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiangxi |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Cheng-Feng |e verfasserin |4 aut | |
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