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Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection.
Huang, Kuo-Yen; Lin, Ming-Shiu; Kuo, Ting-Chun; Chen, Ci-Ling; Lin, Chung-Chih; Chou, Yu-Chi; Chao, Tai-Ling; Pang, Yu-Hao; Kao, Han-Chieh; Huang, Rih-Sheng; Lin, Steven; Chang, Sui-Yuan; Yang, Pan-Chyr.
  • Huang KY; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • Lin MS; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • Kuo TC; Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
  • Chen CL; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • Lin CC; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • Chou YC; Biomedical Translation Research Center (BioTReC), Academia Sinica, Taipei, Taiwan.
  • Chao TL; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
  • Pang YH; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
  • Kao HC; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
  • Huang RS; Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
  • Lin S; Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
  • Chang SY; Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
  • Yang PC; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
EMBO Mol Med ; 13(1): e12828, 2021 01 11.
Article in English | MEDLINE | ID: covidwho-914845
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Internalization / Antibodies, Monoclonal, Humanized / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Experimental Studies / Prognostic study Topics: Variants Limits: Animals / Humans Language: English Journal: EMBO Mol Med Journal subject: Molecular Biology Year: 2021 Document Type: Article Affiliation country: Emmm.202012828

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Internalization / Antibodies, Monoclonal, Humanized / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Experimental Studies / Prognostic study Topics: Variants Limits: Animals / Humans Language: English Journal: EMBO Mol Med Journal subject: Molecular Biology Year: 2021 Document Type: Article Affiliation country: Emmm.202012828