Molecular insights into receptor binding of recent emerging SARS-CoV-2 variants

• Type of Material: Article
• Authors: Pengcheng Han, Chinese Academy of Sciences; Chao Su, Chinese Academy of Sciences; Yanfang Zhang, Chinese Academy of Sciences; Chongzhi Bai, Shanxi Acad Adv Res & Innovat; Anqi Zheng, Chinese Academy of Sciences; Chengpeng Qiao, Chinese Academy of Sciences; Qing Wang, Natl Inst Biol Sci; Sheng Niu, Chinese Academy of Sciences; Qian Chen, Chinese Academy of Sciences; Yuqin Zhang, Chinese Academy of Sciences; Weiwei Li, Chinese Academy of Sciences; Hanyi Liao, Chinese Academy of Sciences; Jing Li, Chinese Academy of Sciences; Zengyuan Zhang, Chinese Academy of Sciences; Hee Cho, Emory University; Mengsu Yang, City University of Hong Kong; Xiaoyu Rong, Chinese Academy of Sciences; Yu Hu, Chinese Academy of Sciences; Niu Huang, National Institute of Biological Sciences, Beijing; Jinghua Yan, Chinese Academy of Sciences; Qihui Wang, Chinese Academy of Sciences; Xin Zhao, Chinese Academy of Sciences; George F Gao, Chinese Academy of Sciences; Jianxun Qi, Chinese Academy of Sciences
• Language: English
• Date: 2021-10-20
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-021-26401-w
• Title of Journal or Parent Work: NATURE COMMUNICATIONS
• Volume: 12
• Issue: 1
• Start Page: 6103
• End Page: 6103
• Grant/Funding Information: G.F.G. is supported by the foundation of the NSFC Innovative Research Group (81621091).; This work was supported by National Key Research and Development Program of China (2021YFC0863300), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29010202, XDB37030204), the intramural special grant for SARS-CoV-2 research from the Chinese Academy of Sciences (CAS), National Key R&D Program of China (2018YFC1200600), and National Natural Science Foundation of China (NSFC, 81922044 and 31800775). Q.H.W. is supported by the Youth Innovation Promotion Association CAS (2018119).
• Keywords: Science & Technology; MUTATIONS; Science & Technology - Other Topics; Multidisciplinary Sciences
• Research Categories: Engineering, Biomedical

Abstract

Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes help identify the key residues facilitating changes in hACE2 binding affinity. Additionally, soluble hACE2 protein efficiently prevent most of the variants pseudoviruses. Our findings provide important molecular information and may help the development of novel therapeutic and prophylactic agents targeting these emerging mutants.