Structural Basis for Accommodation of Emerging B.1.351 and B.1.1.7 Variants by Two Potent SARS-CoV-2 Neutralizing Antibodies

Cerutti, G.; Rapp, M.; Guo, Y.; Bahna, F.; Bimela, J.; Reddem, E. R.; Yu, J.; Wang, P.; Liu, L.; Huang, Y.; Ho, D. D.; Kwong, P. D.; Sheng, Z.; Shapiro, L.

doi:10.1101/2021.02.21.432168

bioRxiv · 10.1101/2021.02.21.432168

Structural Basis for Accommodation of Emerging B.1.351 and B.1.1.7 Variants by Two Potent SARS-CoV-2 Neutralizing Antibodies

Cerutti, G.·Rapp, M.·Guo, Y.·Bahna, F.·Bimela, J.·Reddem, E. R.·Yu, J.·Wang, P.·Liu, L.·Huang, Y.·Ho, D. D.·Kwong, P. D.·Sheng, Z.·Shapiro, L.

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Abstract

Emerging SARS-CoV-2 strains, B.1.1.7 and B.1.351, from the UK and South Africa, respectively show decreased neutralization by monoclonal antibodies and convalescent or vaccinee sera raised against the original wild-type virus, and are thus of clinical concern. However, the neutralization potency of two antibodies, 1-57 and 2-7, which target the receptor-binding domain (RBD) of spike, was unaffected by these emerging strains. Here, we report cryo-EM structures of 1-57 and 2-7 in complex with spike, revealing each of these antibodies to utilize a distinct mechanism to bypass or accommodate RBD mutations. Notably, each antibody represented a response with recognition distinct from those of frequent antibody classes. Moreover, many epitope residues recognized by 1-57 and 2-7 were outside hotspots of evolutionary pressure for both ACE2 binding and neutralizing antibody escape. We suggest the therapeutic use of antibodies like 1-57 and 2-7, which target less prevalent epitopes, could ameliorate issues of monoclonal antibody escape.

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Cerutti, G., Rapp, M., Guo, Y., Bahna, F., Bimela, J., Reddem, E. R., Yu, J., Wang, P., Liu, L., Huang, Y., Ho, D. D., Kwong, P. D., Sheng, Z., Shapiro, L.. 2021-02-22. Structural Basis for Accommodation of Emerging B.1.351 and B.1.1.7 Variants by Two Potent SARS-CoV-2 Neutralizing Antibodies. https://doi.org/10.1101/2021.02.21.432168

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