Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologs
-
Published:2023-12-12
Issue:6
Volume:11
Page:
-
ISSN:2165-0497
-
Container-title:Microbiology Spectrum
-
language:en
-
Short-container-title:Microbiol Spectr
Author:
Yao Weitong123ORCID, Li Yujun2ORCID, Ma Danting24ORCID, Hou Xudong12, Wang Haimin5, Tang Xiaojuan12, Cheng Dechun26, Zhang He12, Du Chengzhi12, Pan Hong12, Li Chao2, Lin Hua7, Sun Mengsi2, Ding Qiang8ORCID, Wang Yingjie2ORCID, Gao Jiali129ORCID, Zhong Guocai125ORCID
Affiliation:
1. School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen, China 2. Shenzhen Bay Laboratory , Shenzhen, China 3. Hubei JiangXia Laboratory , Wuhan, Hubei, China 4. NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University , Tianjin, China 5. Horae Gene Therapy Center, University of Massachusetts Chan Medical School , Worcester, Massachusetts, USA 6. Heilongjiang Academy of Medical Sciences , Harbin, China 7. Biomedical Research Center of South China, Fujian Normal University , Fuzhou, China 8. Center for Infectious Disease Research, School of Medicine, Tsinghua University , Beijing, China 9. Department of Chemistry and Supercomputing Institute, University of Minnesota , Minneapolis, Minnesota, USA
Abstract
ABSTRACT
Spike-receptor interaction is a critical determinant for the host range of coronaviruses. Here, we investigated all the five World Health Organization-designated variants of concern (VOC), including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529), for their Spike receptor-binding domain (RBD)’s interactions with ACE2 orthologs of 18 animal species. We found that, compared to the RBD of an early isolate WHU01, the Alpha RBD has markedly increased affinity to cattle and pig ACE2 proteins and decreased affinity to horse and donkey ACE2 proteins. The RBDs of Beta and Gamma variants have almost completely lost affinity to bat, horse, and donkey ACE2 orthologs. Mainly due to the Q493R and N501Y mutations, the Omicron RBD showed markedly enhanced affinity to mouse ACE2. Molecular dynamic simulations further suggest that Omicron RBDs are optimal for electrostatic interactions with mouse ACE2. Interestingly, the Omicron RBD also showed decreased or complete loss of affinity to eight tested animal ACE2 orthologs, including that of horse, donkey, pig, dog, cat, pangolin, American pika, and bat. The K417N, G496S, and Y505H substitutions were identified as three major contributors that commonly have negative impact on RBD binding to these eight ACE2 orthologs. These findings show that Spike mutations have been continuously shaping SARS-CoV-2’s binding affinities to animal ACE2 orthologs and suggest the importance of surveillance of animal infection by circulating SARS-CoV-2 variants.
IMPORTANCE
Spike-receptor interaction is a critical determinant for the host range of coronaviruses. In this study, we investigated the SARS-CoV-2 WHU01 strain and five WHO-designated SARS-CoV-2 variants of concern (VOCs), including Alpha, Beta, Gamma, Delta, and the early Omicron variant, for their Spike interactions with ACE2 proteins of 18 animal species. First, the receptor-binding domains (RBDs) of Alpha, Beta, Gamma, and Omicron were found to display progressive gain of affinity to mouse ACE2. More interestingly, these RBDs were also found with progressive loss of affinities to multiple ACE2 orthologs. The Omicron RBD showed decreased or complete loss of affinity to eight tested animal ACE2 orthologs, including that of some livestock animals (horse, donkey, and pig), pet animals (dog and cat), and wild animals (pangolin, American pika, and
Rhinolophus sinicus
bat). These findings shed light on potential host range shift of SARS-CoV-2 VOCs, especially that of the Omicron variant.
Funder
Shenzhen Bay Laboratory Shenzhen Municipal Science and Technology Innovation Council Guangdong Pearl River Talent Program National Natural Science Foundation of China 黑龙江省科技厅 | Natural Science Foundation of Heilongjiang Province
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Cell Biology,Microbiology (medical),Genetics,General Immunology and Microbiology,Ecology,Physiology
|
|