@article {Starr2021.02.17.431683, author = {Tyler N. Starr and Allison J. Greaney and Adam S. Dingens and Jesse D. Bloom}, title = {Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016}, elocation-id = {2021.02.17.431683}, year = {2021}, doi = {10.1101/2021.02.17.431683}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for COVID-19. However, ongoing evolution of SARS-CoV-2 can render monoclonal antibodies ineffective. Here we completely map all mutations to the SARS-CoV-2 spike receptor binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escape LY-CoV016). Additionally, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts should diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to antigenic evolution of SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2021/02/22/2021.02.17.431683}, eprint = {https://www.biorxiv.org/content/early/2021/02/22/2021.02.17.431683.full.pdf}, journal = {bioRxiv} }