One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening
| Autor: | Linghang Peng, Paul J. Steiner, Irene M. Francino-Urdaniz, Alison C. Leonard, Shawn Barman, Emily R. Rhodes, Cyrus M. Haas, Fangzhu Zhao, Monica B Kirby, Joseph G. Jardine, Timothy A. Whitehead, Kayla G. Sprenger |
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| Rok vydání: | 2021 |
| Předmět: |
Genetics
Mutation yeast surface display biology Coronavirus disease 2019 (COVID-19) SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Mutant escape mutants medicine.disease_cause Virology Article General Biochemistry Genetics and Molecular Biology Germline Yeast S RBD deep mutational scanning medicine biology.protein neutralizing antibodies Identification (biology) Antibody Neutralizing antibody |
| Zdroj: | bioRxiv article-version (status) pre article-version (number) 1 Cell Reports |
| Popis: | 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. Graphical Abstract Francino-Urdaniz el al. describe a deep mutational scanning method to identify escape mutants on SARS-CoV-2 S RBD. Escape mutants were identified for five neutralizing antibodies elicited from natural infection, revealing hotspots at positions K417, D420, Y421, F486, and Q493 at the periphery of the ACE2 recognition site. |
| Databáze: | OpenAIRE |
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