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 Gabriele Cerutti
A1 Micah Rapp
A1 Yicheng Guo
A1 Fabiana Bahna
A1 Jude Bimela
A1 Eswar R. Reddem
A1 Jian Yu
A1 Pengfei Wang
A1 Lihong Liu
A1 Yaoxing Huang
A1 David D. Ho
A1 Peter D. Kwong
A1 Zizhang Sheng
A1 Lawrence Shapiro
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.