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10.1080/14789450.2020.1833721

http://scihub22266oqcxt.onion/10.1080/14789450.2020.1833721
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suck abstract from ncbi


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pmid33084449      Expert+Rev+Proteomics 2020 ; 17 (9): 633-638
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  • Deep mutagenesis in the study of COVID-19: a technical overview for the proteomics community #MMPMID33084449
  • Procko E
  • Expert Rev Proteomics 2020[Sep]; 17 (9): 633-638 PMID33084449show ga
  • INTRODUCTION: The spike (S) of SARS coronavirus 2 (SARS-CoV-2) engages angiotensin-converting enzyme 2 (ACE2) on a host cell to trigger viral-cell membrane fusion and infection. The extracellular region of ACE2 can be administered as a soluble decoy to compete for binding sites on the receptor-binding domain (RBD) of S, but it has only moderate affinity and efficacy. The RBD, which is targeted by neutralizing antibodies, may also change and adapt through mutation as SARS-CoV-2 becomes endemic, posing challenges for therapeutic and vaccine development. AREAS COVERED: Deep mutagenesis is a Big Data approach to characterizing sequence variants. A deep mutational scan of ACE2 expressed on human cells identified mutations that increase S affinity and guided the engineering of a potent and broad soluble receptor decoy. A deep mutational scan of the RBD displayed on the surface of yeast has revealed residues tolerant of mutational changes that may act as a source for drug resistance and antigenic drift. EXPERT OPINION: Deep mutagenesis requires a selection of diverse sequence variants; an in vitro evolution experiment that is tracked with next-generation sequencing. The choice of expression system, diversity of the variant library and selection strategy have important consequences for data quality and interpretation.
  • |Angiotensin-Converting Enzyme 2/*genetics/*metabolism[MESH]
  • |Binding Sites[MESH]
  • |Mutagenesis[MESH]
  • |Mutation[MESH]
  • |Protein Interaction Domains and Motifs[MESH]
  • |SARS-CoV-2/*genetics[MESH]


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