Author: Francino-Urdaniz, Irene M.; Steiner, Paul J.; Kirby, Monica B.; Zhao, Fangzhu; Haas, Cyrus M.; Barman, Shawn; Rhodes, Emily R.; Leonard, Alison C.; Peng, Linghang; Sprenger, Kayla G.; Jardine, Joseph G.; Whitehead, Timothy A.
Title: One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening Cord-id: h625stz4 Document date: 2021_8_10
ID: h625stz4
Snippet: 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 mutation 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 natu
Document: 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 mutation 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.
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