Humanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infection
Abstract To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, a humanized decoy antibody (ACE2‐Fc fusion protein) was designed to target the interaction between viral spike protein and its cellular receptor, angiotensin‐converting e...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2020-11-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202012828 |
| _version_ | 1827045176401461248 |
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| author | Kuo‐Yen Huang Ming‐Shiu Lin Ting‐Chun Kuo Ci‐Ling Chen Chung‐Chih Lin Yu‐Chi Chou Tai‐Ling Chao Yu‐Hao Pang Han‐Chieh Kao Rih‐Sheng Huang Steven Lin Sui‐Yuan Chang Pan‐Chyr Yang |
| author_facet | Kuo‐Yen Huang Ming‐Shiu Lin Ting‐Chun Kuo Ci‐Ling Chen Chung‐Chih Lin Yu‐Chi Chou Tai‐Ling Chao Yu‐Hao Pang Han‐Chieh Kao Rih‐Sheng Huang Steven Lin Sui‐Yuan Chang Pan‐Chyr Yang |
| author_sort | Kuo‐Yen Huang |
| collection | DOAJ |
| description | Abstract To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, a humanized decoy antibody (ACE2‐Fc fusion protein) was designed to target the interaction between viral spike protein and its cellular receptor, angiotensin‐converting enzyme 2 (ACE2). First, we demonstrated that ACE2‐Fc could specifically abrogate virus replication by blocking the entry of SARS‐CoV‐2 spike‐expressing pseudotyped virus into both ACE2‐expressing lung cells and lung organoids. The impairment of viral entry was not affected by virus variants, since efficient inhibition was also observed in six SARS‐CoV‐2 clinical strains, including the D614G variants which have been shown to exhibit increased infectivity. The preservation of peptidase activity also enables ACE2‐Fc to reduce the angiotensin II‐mediated cytokine cascade. Furthermore, this Fc domain of ACE2‐Fc was shown to activate NK cell degranulation after co‐incubation with Spike‐expressing H1975 cells. These promising characteristics potentiate the therapeutic prospects of ACE2‐Fc as an effective treatment for COVID‐19. |
| first_indexed | 2024-03-07T17:46:31Z |
| format | Article |
| id | doaj.art-fe030031a04a43a49c6198793d078d2e |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T14:20:16Z |
| publishDate | 2020-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-fe030031a04a43a49c6198793d078d2e2024-10-28T08:49:44ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842020-11-0113111910.15252/emmm.202012828Humanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infectionKuo‐Yen Huang0Ming‐Shiu Lin1Ting‐Chun Kuo2Ci‐Ling Chen3Chung‐Chih Lin4Yu‐Chi Chou5Tai‐Ling Chao6Yu‐Hao Pang7Han‐Chieh Kao8Rih‐Sheng Huang9Steven Lin10Sui‐Yuan Chang11Pan‐Chyr Yang12Institute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of MedicineInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaBiomedical Translation Research Center (BioTReC), Academia SinicaDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of MedicineDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of MedicineDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of MedicineInstitute of Biological Chemistry, Academia SinicaInstitute of Biological Chemistry, Academia SinicaDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of MedicineInstitute of Biomedical Sciences, Academia SinicaAbstract To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, a humanized decoy antibody (ACE2‐Fc fusion protein) was designed to target the interaction between viral spike protein and its cellular receptor, angiotensin‐converting enzyme 2 (ACE2). First, we demonstrated that ACE2‐Fc could specifically abrogate virus replication by blocking the entry of SARS‐CoV‐2 spike‐expressing pseudotyped virus into both ACE2‐expressing lung cells and lung organoids. The impairment of viral entry was not affected by virus variants, since efficient inhibition was also observed in six SARS‐CoV‐2 clinical strains, including the D614G variants which have been shown to exhibit increased infectivity. The preservation of peptidase activity also enables ACE2‐Fc to reduce the angiotensin II‐mediated cytokine cascade. Furthermore, this Fc domain of ACE2‐Fc was shown to activate NK cell degranulation after co‐incubation with Spike‐expressing H1975 cells. These promising characteristics potentiate the therapeutic prospects of ACE2‐Fc as an effective treatment for COVID‐19.https://doi.org/10.15252/emmm.202012828ACE2‐FcCOVID‐19decoy antibodySARS‐CoV‐2virus infection |
| spellingShingle | Kuo‐Yen Huang Ming‐Shiu Lin Ting‐Chun Kuo Ci‐Ling Chen Chung‐Chih Lin Yu‐Chi Chou Tai‐Ling Chao Yu‐Hao Pang Han‐Chieh Kao Rih‐Sheng Huang Steven Lin Sui‐Yuan Chang Pan‐Chyr Yang Humanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infection EMBO Molecular Medicine ACE2‐Fc COVID‐19 decoy antibody SARS‐CoV‐2 virus infection |
| title | Humanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infection |
| title_full | Humanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infection |
| title_fullStr | Humanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infection |
| title_full_unstemmed | Humanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infection |
| title_short | Humanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infection |
| title_sort | humanized covid 19 decoy antibody effectively blocks viral entry and prevents sars cov 2 infection |
| topic | ACE2‐Fc COVID‐19 decoy antibody SARS‐CoV‐2 virus infection |
| url | https://doi.org/10.15252/emmm.202012828 |
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