Over the past year thousands of antibodies and nanobodies have been developed to treat and prevent the COVID-19 disease. The emergence of new SARS-CoV-2 variants has decreased the efficacy of vaccines and antibody therapies. Prospective understanding of the set of escape mutants on SARS-CoV-2 Spike that diminish antibody effectiveness would lead to safer, more efficacious antibody therapies against existing and emerging variants. We have developed a method using yeast surface display, high throughput mutagenesis, and deep sequencing to rapidly identify escape mutants on the receptor binding domain of S. With the developed method, we were able to identify mutations that escape neutralizing by common antibodies elicited during natural infection. Some of these mutations, such as E484K, K417N and N501Y, were subsequently identified in emerging variants. We will show the applicability of this method for developing antibodies against other infectious diseases.<br/> <br/>We believe that the science developed during the current pandemic can also be applied to other viruses and future pandemics to come.

Identification of SARS-CoV-2 RBD escape mutants using yeast surface display and deep mutational scanning

ACS Spring 2022

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