RT Journal Article
SR Electronic
T1 Structural Basis for Accommodation of Emerging B.1.351 and B.1.1.7 Variants by Two Potent SARS-CoV-2 Neutralizing Antibodies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.21.432168
DO 10.1101/2021.02.21.432168
A1 Cerutti, Gabriele
A1 Rapp, Micah
A1 Guo, Yicheng
A1 Bahna, Fabiana
A1 Bimela, Jude
A1 Reddem, Eswar R.
A1 Yu, Jian
A1 Wang, Pengfei
A1 Liu, Lihong
A1 Huang, Yaoxing
A1 Ho, David D.
A1 Kwong, Peter D.
A1 Sheng, Zizhang
A1 Shapiro, Lawrence
YR 2021
UL http://biorxiv.org/content/early/2021/02/22/2021.02.21.432168.abstract
AB 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.Competing Interest StatementDDH, YH, JY, LL and PW are inventors of a patent describing some of the antibodies reported on here.