PropertyValue
?:abstract
  • 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.
is ?:annotates of
?:creator
?:doi
  • 10.1080/14789450.2020.1833721
?:doi
?:journal
  • Expert_review_of_proteomics
?:license
  • cc-by-nc-nd
?:pdf_json_files
  • document_parses/pdf_json/1255be96610b4b0bbf06bf283e93e5371df0f474.json
?:pmc_json_files
  • document_parses/pmc_json/PMC7594187.xml.json
?:pmcid
?:pmid
?:pmid
  • 33084449.0
?:publication_isRelatedTo_Disease
is ?:relation_isRelatedTo_publication of
?:sha_id
?:source
  • Medline; PMC
?:title
  • Deep mutagenesis in the study of COVID-19: a technical overview for the proteomics community
?:type
?:year
  • 2020-10-21

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