Receptor binding and complex structures of human ACE2 to spike RBD from Omicron and Delta SARS-CoV-2

Published: 29 December 2021| Version 1 | DOI: 10.17632/s66gf2bbtw.1
Pengcheng Han,
Linjie Li,
Sheng Liu,
Qisheng Wang,
Di Zhang,
Zepeng Xu,
Pu Han,
Xiaomei Li,
qi peng,
Chao Su,
Baihan Huang,
Dedong Li,
Rong Zhang,
Mingxiong Tian,
Lutang Fu,
Yuanzhu Gao,
Xin Zhao,
Kefang Liu,
Jianxun Qi,
George F. Gao,
Peiyi Wang,
Yanfang Zhang


Recent VOC, Omicron (B.1.1.529) has raised many scientific questions and public concern as it obtains unexpected numbers of mutations in the receptor-binding domain (RBD) of the spike protein. Here we tested the human receptor ACE2 (hACE2) binding to the VOC RBDs and resolved the crystal and cryo-EM structures of the Omicron RBD-hACE2 complex and the crystal structure of Delta RBD-hACE2 complex. Unlike Alpha, Beta and Gamma, we found that Omicron RBD binding to hACE2 has similar affinity to the prototype RBD which might due to compensation of multiple mutations for both immune escape and transmissibility. The complex structures of both Omicron-hACE2 and Delta-hACE2 reveal the structural basis of the RBD specific mutations to binding to the hACE2.



Natural Sciences