New methodology for mapping viral mutations that escape antibodies used for the treatment of COVID-19

A new method of mapping viral mutations that “escape” directs clinical antibodies to the detection of mutations in the SARS-CoV-2 virus that allows it to avoid medications, including single mutations an amino acid that completely escapes the Regeneron antibody cocktail. These maps, the authors say, show that the prior identification of escape mutations was infinite. They will also help to immediately explain the impact of mutations cataloged by viral genomic analysis, the authors say.

Several antibodies are used or developed as medications to treat COVID-19. As new SARS-CoV-2 mutations emerge, it is important to predict whether they will be susceptible to antibody treatment. Most anti-SARS-CoV-2 antibodies target the viral receptor-binding domain (RBD), which enables binding to the ACE2 receptor on host cells.

Tyler Starr and colleagues recently developed a scanning method to map how mutations to the RBD affect antibodies detection. Here, Starr and colleagues found this approach to demonstrate how mutations to SARS-CoV-2 RBD affect binding with the antibodies in the REGN-COV2 cocktail and with Eli Lilly antibody LY-CoV016 . The authors focused on mutations to SARS-CoV-2 RBD that do not strongly induce binding to the host receptor (ACE-2), to map how these mutations affect the three anti-SARS-CoV-2 antibodies. The maps identified mutations that escape an antibody binding, including, surprisingly, a single mutant that escapes the two antibodies in a Regeneron antibody cocktail.

To determine whether the escape maps could inform the analysis of viral evolution in infectious humans, the authors examined in-depth series data from a patient with a chronic disease who had been diagnosed. treatment with REGN-COV2 at day 145 after confirmation with COVID-19. The analysis identified stress mutations that arose in this patient. Three of the four escape mutations named by Starr and the team were not identified in the Regeneron viral cell culture selections, the authors said, highlighting the advantage of complete maps as used here.

The complete maps also allowed the researchers to evaluate the existing escape mutations among the SARS-CoV-2 circulation. Having examined all human-acquired SARS-CoV-2 strains available as of January 11, 2021, they report the presence of a large number of RBD mutations that escaped one or more of the antibodies the circulation.