tetano
Editor, Senior Moderator
Cell Rep
. 2023 May 26;42(6):112621.
doi: 10.1016/j.celrep.2023.112621. Online ahead of print. Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail
Amin Addetia[SUP] 1 [/SUP], Young-Jun Park[SUP] 2 [/SUP], Tyler Starr[SUP] 3 [/SUP], Allison J Greaney[SUP] 4 [/SUP], Kaitlin R Sprouse[SUP] 5 [/SUP], John E Bowen[SUP] 5 [/SUP], Sasha W Tiles[SUP] 6 [/SUP], Wesley C Van Voorhis[SUP] 6 [/SUP], Jesse D Bloom[SUP] 3 [/SUP], Davide Corti[SUP] 7 [/SUP], Alexandra C Walls[SUP] 2 [/SUP], David Veesler[SUP] 8 [/SUP]
Affiliations
Continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is eroding antibody responses elicited by prior vaccination and infection. The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated by the REGEN-COV therapeutic monoclonal antibody (mAb) COVID-19 cocktail and the AZD1061 (COV2-2130) mAb. Here, we show that this mutation remodels the receptor-binding site allosterically, thereby altering the epitopes recognized by these three mAbs and vaccine-elicited neutralizing antibodies while remaining functional. Our results demonstrate the spectacular structural and functional plasticity of the SARS-CoV-2 RBD, which is continuously evolving in emerging SARS-CoV-2 variants, including currently circulating strains that are accumulating mutations in the antigenic sites remodeled by the E406W substitution.
Keywords: COVID-19; CP: Immunology; CP: Microbiology; SARS-CoV-2; cryo-EM; monoclonal antibodies; receptor binding domain; spike glycoprotein.
. 2023 May 26;42(6):112621.
doi: 10.1016/j.celrep.2023.112621. Online ahead of print. Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail
Amin Addetia[SUP] 1 [/SUP], Young-Jun Park[SUP] 2 [/SUP], Tyler Starr[SUP] 3 [/SUP], Allison J Greaney[SUP] 4 [/SUP], Kaitlin R Sprouse[SUP] 5 [/SUP], John E Bowen[SUP] 5 [/SUP], Sasha W Tiles[SUP] 6 [/SUP], Wesley C Van Voorhis[SUP] 6 [/SUP], Jesse D Bloom[SUP] 3 [/SUP], Davide Corti[SUP] 7 [/SUP], Alexandra C Walls[SUP] 2 [/SUP], David Veesler[SUP] 8 [/SUP]
Affiliations
- PMID: 37300832
- DOI: 10.1016/j.celrep.2023.112621
Continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is eroding antibody responses elicited by prior vaccination and infection. The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated by the REGEN-COV therapeutic monoclonal antibody (mAb) COVID-19 cocktail and the AZD1061 (COV2-2130) mAb. Here, we show that this mutation remodels the receptor-binding site allosterically, thereby altering the epitopes recognized by these three mAbs and vaccine-elicited neutralizing antibodies while remaining functional. Our results demonstrate the spectacular structural and functional plasticity of the SARS-CoV-2 RBD, which is continuously evolving in emerging SARS-CoV-2 variants, including currently circulating strains that are accumulating mutations in the antigenic sites remodeled by the E406W substitution.
Keywords: COVID-19; CP: Immunology; CP: Microbiology; SARS-CoV-2; cryo-EM; monoclonal antibodies; receptor binding domain; spike glycoprotein.