Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

By Tyler N. Starr, Allison J. Greaney, Amin Addetia, William W. Hannon, M. Choudhary, A. Dingens, Jonathan Z. Li, Jesse D. Bloom. bioRxiv, 2020

627 citations recorded by the source corpus.

Antibodies are becoming a frontline therapy for SARS-CoV-2, but the risk of viral evolutionary escape remains unclear. Here we map how all mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in Regeneron’s REGN-COV2 cocktail and Eli Lilly’s LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2, as well as in lab viral escape selections. Finally, the maps reveal that mutations escaping each individual antibody are already present in circulating SARS-CoV-2 strains. Overall, these complete escape maps enable immediate interpretation of the consequences of mutations observed during viral surveillance.

Subfields: Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5fb96597a808d0bdf3e4203c08f942ff49d5c51e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

1. Jesse D. Bloom

In Molecular Biology

1. Tyler N. Starr
2. K. H. Crawford
3. Allison J. Greaney
4. Jesse D. Bloom

Citations in the corpus

• Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies (2021, methodology): “The library covered nearly all possible single amino-acid mutations to the RBD (Starr et al., 2020b) .”
• A human coronavirus evolves antigenically to escape antibody immunity (2020, background): “While it is impossible to know if SARS-CoV-2 will evolve similarly to 229E, it is ominous that mutations affecting neutralization by antibodies or sera are already present at low frequencies among circulating SARS-CoV-2 (Greaney et al., 2020; Kemp, 2020; Liu et al., 2020b; McCarthy et al., 2020; Sta”