SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016

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Science

4/8/2021


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DR Bloom had recently published a good study on latest fast spreading sarscov2 variants that escape monoclonal antibody cocktails. Some excerpts from “Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016

By Tyler N. Starr, Allison J. Greaney Adam S. Dingens, Jesse D. Bloom

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. Of particular note, the B.1.351 (a.k.a. 20H/501Y.V2) [10] and P.1 (a.k.a. 20J/501Y.V3) [12] lineages contain combinations of mutations (E484K and K417N/T) that individually escape each antibody (Fig. 2B), suggesting that the LY-CoV555+LY-CoV016 cocktail may be ineffective against these lineages. In addition, the B.1.429 lineage (a.k.a. 20C/CAL.20C) that has risen to high frequency in southern California contains L452R [13], which escapes LY-CoV555 (Fig. 2B). We also note that single mutations that escape both antibodies (Q493R and Q493K) have been observed in a handful of sequenced isolates (Fig. 2A). https://www.biorxiv.org/content/10.1101/2021.02.17.431683v1

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