RT Journal Article
SR Electronic
T1 Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.27.493682
DO 10.1101/2022.05.27.493682
A1 Xiaoman Li
A1 Yongbing Pan
A1 Qiangling Yin
A1 Zejun Wang
A1 Sisi Shan
A1 Laixing Zhang
A1 Jinfang Yu
A1 Yuanyuan Qu
A1 Lina Sun
A1 Fang Gui
A1 Jia Lu
A1 Zhaofei Jing
A1 Wei Wu
A1 Tao Huang
A1 Xuanling Shi
A1 Jiandong Li
A1 Xinguo Li
A1 Dexin Li
A1 Shiwen Wang
A1 Maojun Yang
A1 Linqi Zhang
A1 Kai Duan
A1 Mifang Liang
A1 Xiaoming Yang
A1 Xinquan Wang
YR 2022
UL http://biorxiv.org/content/early/2022/05/27/2022.05.27.493682.abstract
AB SARS-CoV-2 variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding working mechanisms and developing therapeutic agents. In this study, we characterized previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-EM structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.Competing Interest StatementThe authors have declared no competing interest.