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10.1038/s41594-020-00549-3

http://scihub22266oqcxt.onion/10.1038/s41594-020-00549-3
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33432247!7895301!33432247
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suck abstract from ncbi


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pmid33432247      Nat+Struct+Mol+Biol 2021 ; 28 (2): 202-209
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  • A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent #MMPMID33432247
  • Xiao T; Lu J; Zhang J; Johnson RI; McKay LGA; Storm N; Lavine CL; Peng H; Cai Y; Rits-Volloch S; Lu S; Quinlan BD; Farzan M; Seaman MS; Griffiths A; Chen B
  • Nat Struct Mol Biol 2021[Feb]; 28 (2): 202-209 PMID33432247show ga
  • Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a membrane-bound carboxypeptidase that forms a dimer and serves as the cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 is also a key negative regulator of the renin-angiotensin system that modulates vascular functions. We report here the properties of a trimeric ACE2 ectodomain variant, engineered using a structure-based approach. The trimeric ACE2 variant has a binding affinity of ~60 pM for the spike protein of SARS?CoV?2 (compared with 77 nM for monomeric ACE2 and 12-22 nM for dimeric ACE2 constructs), and its peptidase activity and the ability to block activation of angiotensin II receptor type 1 in the renin-angiotensin system are preserved. Moreover, the engineered ACE2 potently inhibits SARS?CoV?2 infection in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.
  • |*COVID-19 Drug Treatment[MESH]
  • |Angiotensin-Converting Enzyme 2/*chemistry/genetics/therapeutic use[MESH]
  • |Antiviral Agents/*chemistry/therapeutic use[MESH]
  • |Cryoelectron Microscopy[MESH]
  • |Humans[MESH]
  • |Models, Molecular[MESH]
  • |Protein Engineering[MESH]
  • |Protein Multimerization[MESH]
  • |Recombinant Proteins/chemistry/genetics/therapeutic use[MESH]


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