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10.1038/s41598-021-91809-9

http://scihub22266oqcxt.onion/10.1038/s41598-021-91809-9
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suck abstract from ncbi


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pmid34140558      Sci+Rep 2021 ; 11 (1): 12740
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  • An ACE2 Triple Decoy that neutralizes SARS-CoV-2 shows enhanced affinity for virus variants #MMPMID34140558
  • Tanaka S; Nelson G; Olson CA; Buzko O; Higashide W; Shin A; Gonzalez M; Taft J; Patel R; Buta S; Richardson A; Bogunovic D; Spilman P; Niazi K; Rabizadeh S; Soon-Shiong P
  • Sci Rep 2021[Jun]; 11 (1): 12740 PMID34140558show ga
  • The SARS-CoV-2 variants replacing the first wave strain pose an increased threat by their potential ability to escape pre-existing humoral protection. An angiotensin converting enzyme 2 (ACE2) decoy that competes with endogenous ACE2 for binding of the SARS-CoV-2 spike receptor binding domain (S RBD) and inhibits infection may offer a therapeutic option with sustained efficacy against variants. Here, we used Molecular Dynamics (MD) simulation to predict ACE2 sequence substitutions that might increase its affinity for S RBD and screened candidate ACE2 decoys in vitro. The lead ACE2(T27Y/H34A)-IgG(1)F(C) fusion protein with enhanced S RBD affinity shows greater live SARS-CoV-2 virus neutralization capability than wild type ACE2. MD simulation was used to predict the effects of S RBD variant mutations on decoy affinity that was then confirmed by testing of an ACE2 Triple Decoy that included an additional enzyme activity-deactivating H374N substitution against mutated S RBD. The ACE2 Triple Decoy maintains high affinity for mutated S RBD, displays enhanced affinity for S RBD N501Y or L452R, and has the highest affinity for S RBD with both E484K and N501Y mutations, making it a viable therapeutic option for the prevention or treatment of SARS-CoV-2 infection with a high likelihood of efficacy against variants.
  • |*Amino Acid Substitution[MESH]
  • |*Molecular Dynamics Simulation[MESH]
  • |Amino Acid Sequence[MESH]
  • |Angiotensin-Converting Enzyme 2/*chemistry/*metabolism[MESH]
  • |Antiviral Agents/*pharmacology[MESH]
  • |COVID-19/*metabolism/virology[MESH]
  • |Drug Discovery/*methods[MESH]
  • |Humans[MESH]
  • |Mutation[MESH]
  • |Protein Binding/drug effects[MESH]
  • |Protein Domains/genetics[MESH]
  • |SARS-CoV-2/*metabolism[MESH]
  • |Signal Transduction/*drug effects[MESH]
  • |Spike Glycoprotein, Coronavirus/metabolism[MESH]


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