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One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening
Irene Francino Urdaniz; Paul J Steiner; Monica Kirby; Fangzhu Zhao; Cyrus M Haas; Shawn Barman; Emily R Rhodes; Linghang Peng; Kayla Sprenger; Joseph Jardine; Timothy A Whitehead.
Affiliation
  • Irene Francino Urdaniz; University of Colorado, Boulder
  • Paul J Steiner; University of Colorado, Boulder
  • Monica Kirby; University of Colorado, Boulder
  • Fangzhu Zhao; The Scripps Research Institute
  • Cyrus M Haas; University of Colorado, Boulder
  • Shawn Barman; The Scripps Research Institute
  • Emily R Rhodes; University of Colorado, Boulder
  • Linghang Peng; The Scripps Research Institute
  • Kayla Sprenger; University of Colorado, Boulder
  • Joseph Jardine; International AIDS Vaccine Initiative
  • Timothy A Whitehead; University of Colorado, Boulder
Preprint in English | bioRxiv | ID: ppbiorxiv-435309
ABSTRACT
The potential emergence of SARS-CoV-2 Spike (S) escape mutants is a threat to reduce the efficacy of existing vaccines and neutralizing antibody (nAb) therapies. An understanding of the antibody/S escape mutations landscape is urgently needed to preemptively address this threat. Here we describe a rapid method to identify escape mutants for nAbs targeting the S receptor binding site. We identified escape mutants for five nAbs, including three from the public germline class VH3-53 elicited by natural COVID-19 infection. Escape mutations predominantly mapped to the periphery of the ACE2 recognition site on the RBD with K417, D420, Y421, F486, and Q493 as notable hotspots. We provide libraries, methods, and software as an openly available community resource to accelerate new therapeutic strategies against SARS-CoV-2. One Sentence SummaryWe present a facile method to identify antibody escape mutants on SARS-CoV-2 S RBD.
License
cc_by_nc_nd
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
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