A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent in vitro
Abstract Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that forms a dimer and serves as the cellular receptor for SARS-CoV-2. It is also a key negative regulator of the renin-angiotensin system (RAS), conserved in mammals, which modulates vascular functions. We report here the properties of a trimeric ACE2 variant, created by a structure-based approach, with binding affinity of ~60 pM for the spike (S) protein of SARS-CoV-2, while preserving the wildtype peptidase activity as well as the ability to block activation of angiotensin II receptor type 1 in the RAS. Moreover, the engineered ACE2 potently inhibits infection of SARS-CoV-2 in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 19. Nov. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xiao, Tianshu [VerfasserIn] |
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| doi: |
10.1101/2020.09.18.301952 |
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| PPN (Katalog-ID): |
XBI01880232X |
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| 245 | 1 | 0 | |a A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent in vitro |
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| 520 | |a Abstract Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that forms a dimer and serves as the cellular receptor for SARS-CoV-2. It is also a key negative regulator of the renin-angiotensin system (RAS), conserved in mammals, which modulates vascular functions. We report here the properties of a trimeric ACE2 variant, created by a structure-based approach, with binding affinity of ~60 pM for the spike (S) protein of SARS-CoV-2, while preserving the wildtype peptidase activity as well as the ability to block activation of angiotensin II receptor type 1 in the RAS. Moreover, the engineered ACE2 potently inhibits infection of SARS-CoV-2 in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Lu, Jianming |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Rebecca I. |e verfasserin |4 aut | |
| 700 | 1 | |a McKay, Lindsay G.A. |e verfasserin |4 aut | |
| 700 | 1 | |a Storm, Nadia |e verfasserin |4 aut | |
| 700 | 1 | |a Lavine, Christy L. |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Hanqin |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Yongfei |e verfasserin |4 aut | |
| 700 | 1 | |a Rits-Volloch, Sophia |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Shen |e verfasserin |4 aut | |
| 700 | 1 | |a Quinlan, Brian D. |e verfasserin |4 aut | |
| 700 | 1 | |a Farzan, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Seaman, Michael S. |e verfasserin |4 aut | |
| 700 | 1 | |a Griffiths, Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Bing |e verfasserin |4 aut | |
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