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An ACE2 Microbody Containing a Single Immunoglobulin Fc Domain Is a Potent Inhibitor of SARS-CoV-2.
Tada, Takuya; Fan, Chen; Chen, Jennifer S; Kaur, Ramanjit; Stapleford, Kenneth A; Gristick, Harry; Dcosta, Belinda M; Wilen, Craig B; Nimigean, Crina M; Landau, Nathaniel R.
  • Tada T; Department of Microbiology, NYU Langone Medical Center, New York, NY 10016, USA.
  • Fan C; Department of Anesthesiology, Weill Cornell Medical College, New York, NY 10065, USA.
  • Chen JS; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Kaur R; Department of Microbiology, NYU Langone Medical Center, New York, NY 10016, USA.
  • Stapleford KA; Department of Microbiology, NYU Langone Medical Center, New York, NY 10016, USA.
  • Gristick H; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Dcosta BM; Department of Microbiology, NYU Langone Medical Center, New York, NY 10016, USA.
  • Wilen CB; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Nimigean CM; Department of Anesthesiology, Weill Cornell Medical College, New York, NY 10065, USA.
  • Landau NR; Department of Microbiology, NYU Langone Medical Center, New York, NY 10016, USA. Electronic address: nathaniel.landau@med.nyu.edu.
Cell Rep ; 33(12): 108528, 2020 12 22.
Article in English | MEDLINE | ID: covidwho-978234
ABSTRACT
Soluble forms of angiotensin-converting enzyme 2 (ACE2) have recently been shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We report on an improved soluble ACE2, termed a "microbody," in which the ACE2 ectodomain is fused to Fc domain 3 of the immunoglobulin (Ig) heavy chain. The protein is smaller than previously described ACE2-Ig Fc fusion proteins and contains an H345A mutation in the ACE2 catalytic active site that inactivates the enzyme without reducing its affinity for the SARS-CoV-2 spike. The disulfide-bonded ACE2 microbody protein inhibits entry of SARS-CoV-2 spike protein pseudotyped virus and replication of live SARS-CoV-2 in vitro and in a mouse model. Its potency is 10-fold higher than soluble ACE2, and it can act after virus bound to the cell. The microbody inhibits the entry of ß coronaviruses and virus with the variant D614G spike. The ACE2 microbody may be a valuable therapeutic for coronavirus disease 2019 (COVID-19) that is active against viral variants and future coronaviruses.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Immunoglobulin Fc Fragments / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / Microbodies Topics: Variants Limits: Animals / Female / Humans / Male Language: English Journal: Cell Rep Year: 2020 Document Type: Article Affiliation country: J.celrep.2020.108528

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Immunoglobulin Fc Fragments / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / Microbodies Topics: Variants Limits: Animals / Female / Humans / Male Language: English Journal: Cell Rep Year: 2020 Document Type: Article Affiliation country: J.celrep.2020.108528