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10.1038/s41467-021-24013-y http://scihub22266oqcxt.onion/10.1038/s41467-021-24013-y 34155214!8217473!34155214     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Commun 2021 ; 12 (1): 3802 Nephropedia Template TP {{tp|p=34155214|t=2021. Engineered ACE2 receptor therapy overcomes mutational escape of SARS-CoV-2 |pdf=|usr=}}{{34155214}} gab.com Text Engineered ACE2 receptor therapy overcomes mutational escape of SARS-CoV-2 JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=34155214 #FOAvip SARS-CoV-2 has mutated during the global pandemic leading to viral adaptation to medications and vaccinations. Here we describe an engineered human virus receptor, ACE2, by mutagenesis and screening for binding to the receptor binding domain (RBD). Three cycles of random mutagenesis and cell sorting achieved sub-nanomolar affinity to RBD. Our structural data show that the enhanced affinity comes from better hydrophobic packing and hydrogen-bonding geometry at the interface. Additional disulfide mutations caused the fixing of a closed ACE2 conformation to avoid off-target effects of protease activity, and also improved structural stability. Our engineered ACE2 neutralized SARS-CoV-2 at a 100-fold lower concentration than wild type; we also report that no escape mutants emerged in the co-incubation after 15 passages. Therapeutic administration of engineered ACE2 protected hamsters from SARS-CoV-2 infection, decreased lung virus titers and pathology. Our results provide evidence of a therapeutic potential of engineered ACE2. Twit Text FOAVip Engineered ACE2 receptor therapy overcomes mutational escape of SARS-CoV-2 ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=34155214 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34155214 #FOAvip English Wikipedia <ref>{{Cite pmid|34155214}}</ref> Engineered ACE2 receptor therapy overcomes mutational escape of SARS-CoV-2 #MMPMID34155214 Higuchi Y; Suzuki T; Arimori T; Ikemura N; Mihara E; Kirita Y; Ohgitani E; Mazda O; Motooka D; Nakamura S; Sakai Y; Itoh Y; Sugihara F; Matsuura Y; Matoba S; Okamoto T; Takagi J; Hoshino A Nat Commun 2021[Jun]; 12 (1): 3802 PMID34155214show ga SARS-CoV-2 has mutated during the global pandemic leading to viral adaptation to medications and vaccinations. Here we describe an engineered human virus receptor, ACE2, by mutagenesis and screening for binding to the receptor binding domain (RBD). Three cycles of random mutagenesis and cell sorting achieved sub-nanomolar affinity to RBD. Our structural data show that the enhanced affinity comes from better hydrophobic packing and hydrogen-bonding geometry at the interface. Additional disulfide mutations caused the fixing of a closed ACE2 conformation to avoid off-target effects of protease activity, and also improved structural stability. Our engineered ACE2 neutralized SARS-CoV-2 at a 100-fold lower concentration than wild type; we also report that no escape mutants emerged in the co-incubation after 15 passages. Therapeutic administration of engineered ACE2 protected hamsters from SARS-CoV-2 infection, decreased lung virus titers and pathology. Our results provide evidence of a therapeutic potential of engineered ACE2. |*COVID-19 Drug Treatment[MESH] |*Mutation[MESH] |Angiotensin-Converting Enzyme 2/*genetics/metabolism/*pharmacology[MESH] |Animals[MESH] |COVID-19/metabolism/virology[MESH] |Cells, Cultured[MESH] |Cricetinae[MESH] |Crystallography, X-Ray[MESH] |Disease Models, Animal[MESH] |Humans[MESH] |Male[MESH] |Molecular Dynamics Simulation[MESH] |Protein Binding[MESH] |Protein Engineering/methods[MESH] |SARS-CoV-2/*drug effects/isolation & purification/metabolism[MESH]Engineered ACE2 receptor therapy overcomes mutational escape of SARS-C(epmc).pdf DeepDyve Pubget Overpricing